Search results for: diabetic mice

Authors: N. Uchegbu Nneka

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This study was conducted to investigate the effect of the antioxidant activity of germinated African Yam Bean (AYB) on oxidative stress markers in alloxan-induced diabetic rat. Rats were randomized into three groups; control, diabetic and germinated AYB–treated diabetic rats. The Total phenol and flavonoid content and DPPH radical scavenging activity before and after germination were investigated. The glucose level, lipid peroxidation and reduced glutathione of the animals were also determined using the standard technique for four weeks. Germination increased the total phenol, flavonoid and antioxidant activity of AYB extract by 19.14%, 32.28%, and 57.25% respectively. The diabetic rats placed on germinated AYB diet had a significant decrease in the blood glucose and lipid peroxidation with a corresponding increase in glutathione (p<0.05). These results demonstrate that consumption of germinated AYB can be a good dietary supplement in inhibiting hyperglycemia/hyperlipidemia and the prevention of diabetic complication associated with oxidative stress.

Keywords: African yam bean, antioxidant, diabetes, total phenol

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Authors: Guo Yu, Haoming Ma, Peiru Zhou

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BACKGROUND: In addition to hyperglycemia, hypoglycemia, and glycemic variability, a decrease in the time in the targeted blood glucose range (TIR) may be associated with an increased risk of death for critically ill patients. However, the relationship between the TIR and mortality may be influenced by the presence of diabetes and glycemic variability. METHODS: A total of 998 diabetic and non-diabetic patients with severe diseases in the ICU were selected for this retrospective analysis. The TIR is defined as the percentage of time spent in the target blood glucose range of 3.9–10.0 mmol/L within 24 hours. The relationship between TIR and in-hospital in diabetic and non-diabetic patients was analyzed. The effect of glycemic variability was also analyzed. RESULTS: The binary logistic regression model showed that there was a significant association between the TIR as a continuous variable and the in-hospital death of severely ill non-diabetic patients (OR=0.991, P=0.015). As a classification variable, TIR≥70% was significantly associated with in-hospital death (OR=0.581, P=0.003). Specifically, TIR≥70% was a protective factor for the in-hospital death of severely ill non-diabetic patients. The TIR of severely ill diabetic patients was not significantly associated with in-hospital death; however, glycemic variability was significantly and independently associated with in-hospital death (OR=1.042, P=0.027). Binary logistic regression analysis of comprehensive indices showed that for non-diabetic patients, the C3 index (low TIR & high CV) was a risk factor for increased mortality (OR=1.642, P<0.001). In addition, for diabetic patients, the C3 index was an independent risk factor for death (OR=1.994, P=0.008), and the C4 index (low TIR & low CV) was independently associated with increased survival. CONCLUSIONS: The TIR of non-diabetic patients during ICU hospitalization was associated with in-hospital death even after adjusting for disease severity and glycemic variability. There was no significant association between the TIR and mortality of diabetic patients. However, for both diabetic and non-diabetic critically ill patients, the combined effect of high TIR and low CV was significantly associated with ICU mortality. Diabetic patients seem to have higher blood glucose fluctuations and can tolerate a large TIR range. Both diabetic and non-diabetic critically ill patients should maintain blood glucose levels within the target range to reduce mortality.

Keywords: severe disease, diabetes, blood glucose control, time in targeted blood glucose range, glycemic variability, mortality

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Authors: Eun-Young Kwon, Myung-Sook Choi, Su-Jung Cho, Ji-Young Choi, So Young Kim, Youngji Han

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Overweight and obesity have been linked to a low-grade chronic inflammatory response and an increased risk of developing metabolic syndrome including insulin resistance, type 2 diabetes mellitus and certain types of cancers. Luteolin is a dietary flavonoid with anti-inflammatory, anti-oxidant, anti-cancer and anti-diabetic properties. However, little is known about the detailed mechanism associated with the effect of luteolin on inflammation-related obesity and its complications. The aim of the present study was to reveal the anti-diabetic effect of luteolin in diet-induced obesity mice using “transcriptomics” tool. Thirty-nine male C57BL/6J mice (4-week-old) were randomly divided into 3 groups and were fed normal diet, high-fat diet (HFD, 20% fat) and HFD+0.005% (w/w) luteolin for 16 weeks. Luteolin improved insulin resistance, as measured by HOMA-IR and glucose tolerance, along with preservation action of pancreatic β-cells, compared to the HFD group. Luteoiln was significantly decreased the levels of leptin and ghrelin that play a pivotal role in energy balance, and the macrophage low-grade inflammation marker sCD163 (soluble Cd antigen 163) in plasma. Activities of hepatic anti-oxidant enzymes (catalase and glutathione peroxidase) were increased, while the levels of plasma transaminase (GOT and GPT) and oxidative damage markers (hepatic mitochondria H2O2 and TBARS) were markedly decreased by luteolin supplementation. In addition, luteolin increased oxidative capacity and fatty acid utilization by presenting decrease in enzyme activities of citrate synthase, cytochrome C oxidase and β-hydroxyacyl CoA dehydrogenase and UCP3 gene expression compared to high-fat diet. Moreover, our microarray results of muscle also revealed down-regulated gene expressions associated with TCA cycle by HFD were reversed to normal level by luteolin treatment. Taken together, our results indicate that luteolin is one of bioactive components for improving insulin resistance by increasing oxidative capacity, modulating anti-oxidant metabolism and suppressing inflammatory signaling cascades in diet-induced obese mice. These results provide possible therapeutic targets for prevention and treatment of diet-induced obesity and its complications.

Keywords: anti-oxidant metabolism, diabetes, luteolin, oxidative capacity

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Authors: Ji Hyung Park, Dong-Hyun Seo, Young-Jin Jung, Han Sung Kim

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The aim of this study is to evaluate the effects of the laser and partial vibration stimulation on the mice tibia with morphological characteristics. Twenty female C57BL/6 mice (12 weeks old) were used for the experiment. The study was carried out on four groups of animals each consisting of five mice. Four groups of mice were ovariectomized. Animals were scanned at 0 and 2 weeks after ovariectomy by using micro-computed tomography to estimate morphological characteristics of tibial trabecular bone. Morphological analysis showed that structural parameters of multi-stimuli group appear significantly better phase in BV/TV, BS/BV, Tb.Th, Tb.N, Tb.Sp, and Tb.pf than single stimulation groups. However, single stimulation groups didn’t show significant effect on tibia with Sham group. This study suggests that multi-stimuli may restrain the change as the degenerate phase on osteoporosis in the mice tibia.

Keywords: laser, partial vibration, osteoporosis, in-vivo micro-CT, mice

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Authors: Tahmineh Hasanzadeh, Afshin Farahbakhsh

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There is some report about the hypoglycemic effect of Juglans rejia L. leaf in alloxan induced diabetic rats and hypoglycemic effect of its fruit peel administered intraperitoneally.In Iranian traditional medicine, septum of walnut shell (SWS) was recommended to reduce blood glucose. For this purpose, 41 male bulb/C mice 25-30 gm were divided into five groups. All the animals received IP injection of streptozotocin (STZ) (220 mg/kg). Two weeks later, the diabetic animals were received daily oral treatment of normal saline and aqueous extract of SWS (200, 400, 600 and 800 mg/kg) respectively for four weeks. Blood samples were taken from retro orbital sinus before the start of the experiment and repeated each two weeks. At the end of the experiment, the animals were sacrificed and the pancreatic tissues were fixed, prepared and stained by Hematoxylin-Eosin for light microscope studies. The results showed that in each group, the SWS extract reduced blood glucose in a long time (p < 0.05). metabolic extract in STZ- induced diabetic rats, which was accompanied by the hypoglycemic effect of leaf extract. However, this effect should be determined with scientific researches. Therefore, the aim of this study is to evaluate the effect of the aqueous extract of SWS on blood glucose and histopathological structure of pancreas.

Keywords: septum of walnut, blood glucose, pancreas, diabetes, walnut leaf, walnut peel, insulin

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Authors: Anne R. Fernandez, Mohammad Akmal Adnan, Tanes Prasat, Indu Bala Jaganath, Brian Kirby, Kamalan Jeevaratnam

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Introduction: Plants from the Phyllantus genus have been used indigenously for the treatment of a variety of ailments for generations. A cocktail of phytonutrients prepared from a plant of the genus Phyllanthus has demonstrated the potential to alleviate ailments which include cardiovascular disorders. In this study, we investigated the cholesterol modulating properties of a highly purified proprietary extract of a Phyllanthus species in hypercholesteraemic mice. Methods: Hypercholesteraemia was induced in ICR mice by ad-libitum feeding of high fat diet daily for six weeks. The mice were then divided into 3 groups and force fed with 10mg/kg of atorvastatin, 200mg/kg of the proprietary Phyllanthus extract and water respectively. Blood samples were taken at the end of fourth week of treatment by a tail prick. At the end of the eighth week of treatment, mice were sacrificed and serum levels of total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides were measured. Results: The mean cholesterol levels in the mice fed with high fat diet were 44% (p < 0.05) higher than the mice on normal diet thus validating the model developed. The plasma HDL was significantly elevated in mice treated with the formulation (p ˂ 0.05) in comparison to the statin-treated and control mice. The total cholesterol levels in the mice treated with the proprietary extract were reduced significantly (p < 0.05) at the end of 4 weeks of treatment in comparison to the mice treated with atorvastatin. By the end of 8 weeks of treatment, there was no significant difference in the cholesterol levels of the mice in all groups. Conclusion: These results demonstrate that this proprietary extract from Phyllanthus species has the beneficial effect of reducing total cholesterol level more rapidly than atorvastatin and increasing HDL levels. Since an increase in the HDL cholesterol can reduce the risk of heart disease, this proprietary extract is a useful and safe therapeutic option compared to atorvastatin.

Keywords: high-density lipoprotein, hypercholesteraemic mice model, ICR mice, Phyllanthus spp.

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Authors: Ali Kassem, Mohamed Alsenbasy, Ahmed Nagaah

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Background: Diabetic foot is one of the often neglected complications of diabetes mellitus It was reported that patients of diabetic foot ulcer (DFU) have considerable morbidity and mortality. Due to arterial abnormalities, diabetic neuropathy, as well as the tendency to delayed wound healing, foot infection and or gangrene is relatively common in diabetic patients. Foot related problems are responsible for up to 50% of diabetic related hospital admissions. Aim of work: The aim of the present study is to assess the risk factors for DFU in diabetic patients attending Sohag University Hospitals (Upper Egypt) Material and methods: The present study includes 100 diabetic foot patients attending the diabetic outpatient clinic of Sohag University Hospitals. For all of the studied patients the following were done: Full medical history and clinical examination; thorough foot examination; Laboratory tests including: Blood glucose level, HBA1c, serum lipids and renal function tests, ECG and Echocardiography, Doppler study on the lower limbs. Results: Sixty eight percent of the affected patients were males versus 32 % female patients. All male patients and none of the female were smoker. Seventy nine percent of patients were living in rural areas versus 14 % in urban areas. Duration of diabetes was more than 12 years in 74%, less than 12 years in 26% of patients. Fifty percent of patients have associated hypertension, 46% have dyslipidemia, 18% have ischemic heart disease or old myocardial infarction and 8% have impaired renal function. History of previous foot ulcers was reported in 11 % and foot amputation in 2% of patients. Conclusion: Male gender, low socioeconomic status, smoking, long duration of diabetes, other cardiovascular risk factors particularly hypertension and previous history of foot ulceration are the major risk factors for diabetic foot in our locality.

Keywords: diabetic foot, diabetic neuropathy, foot gangrene, risk factors for diabetic complications

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Authors: Xuan Li, Xiaobing Cui, Nan Meng, Shuangshuang Guo, Lingling Wang

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Objective: To investigate the influence of Paeonol on diabetic nephropathy progression in streptozocin (STZ) -induced diabetic rats. Method Male Wistar rats were injected STZ 30mg.kg-1 combined with Freund's complete adjuvant (CFA) 0.1mL/rat once a week for three weeks. The diabetic rats were treated with Paenol for 13 weeks. At the end of the experiments, the rats were anesthetized. Serum and the kidney were collected. Serum superoxide dismutase (SOD) activity, malondialdehyde (MDA), blood urea nitrogen (BUN), creatinine (Cr) and total cholesterol (Chol) level were detected; kidney paraffin sections were prepared and HE and PAS staining sections were used to evaluate the pathology changes of the kidney. Immunohistochemical analysis was used to observe the expression of VEGF and fibernectin expression in the kidney. Result The blood glucose level remained over 16mmol. L-1 for 13 weeks and the ECM accumulated in the diabetic kidney apparently. Paeonol treatment increased serum SOD activity, however, MDA, BUN, Cr, and Chol level was decreased by paeonol treatment. VEGF and fibernectin expression were increased significantly in the DN rats and paeonol treatment ameliorated the overexpression. Conclusion: paeonol prevented the progression of DN.

Keywords: paeonol, STZ, diabetic nephropathy, fibernectin expression, kidney paraffin sections

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Authors: Yao Huang, Hongjie Yu, Fangrong Xu, Longbiao Cai, Qiqiang He

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The Klotho gene has been found to be involved in cardiovascular health, and epigenetic mechanism has risen as good candidates to understand the role of lifestyle factors in obesity. The aim of this study was to investigate the effect of exercise intervention on the expression and DNA methylation of Klotho gene in high-fat diet induced obese mice. C57BL/6 male mice were fed a normal diet (ND) or a high-fat diet (HFD) for 12 weeks. HFD induced obese mice were divided into secondary group (SED) and exercise group (EX) randomly. The treadmill exercise was performed in EX group for 8 weeks. The expression and DNA methylation of Klotho were evaluated by Western blot, RT-PCR, and Methylation-specific PCR. Results indicated that Klotho protein and mRNA expression were significantly lower in the SED group than those in the ND and EX groups (P<0.01), whereas no significant difference, was found between ND group and EX group (P>0.05). Furthermore, mice in the ND group and SED group showed significantly lower levels of completely methylated Klotho DNA in ND group (0%) and SED group (50%) compared with the EX group (90%), and unmethylated Klotho DNA level in ND group (80%) was significantly higher than those in the SED (0%) and EX (0%) groups. These results suggested that exercise leads to increased Klotho expression and reduced Klotho DNA methylation level in HFD induced obese mice.

Keywords: DNA methylation, exercise intervention, klotho, obese mice

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Authors: Daniel P. Kisangau, Ken M. Hosea, Herbert V. M. Lyaruu, Cosam C. Josep, Zakaria H. Mbwambo, Pax J. Masimba

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Crude extracts of Dracaena steudneri bark (DSB), Sapium ellipticum bark (SEB) and Capparis erythrocarpos root (CER) were investigated for their antifungal activity in immunocompromised mice infected with Candida albicans in an in vivo mice infection model. The results revealed a substantial dose dependency in all treatments given, with mice survival to the end of the experiment correlating well to the dose levels. At a dose of 400 mg/kg, C. erythrocarpos was the most effective with mice survival of 60% and organ burden clearance ranging from 64.0%-99.9% (P<0.0001) in all treatments. At the same dose, the least effective plant was S. ellipticum which had a mice survival of 20% and organ burden clearance ranging from 78.0%-96.6 (P>0.05). Mice survival for D. steudneri was 30% with organ burden clearance ranging from 89.0%-99.9% (P<0.05). All mice receiving no active treatment died before ten days post infection. In all treatment groups, there was a steady decline in mean weights of mice immediately after immunosuppression followed by gradual recovery in some cases which appeared to be dose dependent a few days post infection. Thus, extracts of D. steudneri and C. erythrocarpos portrayed the most significant potential as sources of antifungal drugs.

Keywords: antifungal activity, medicinal plants, candida albicans, East Africa

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Authors: Bawa Inalegwu, Jacob A. Jato, Ovye Akyengo, John Akighir

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All humans will experience some type of wound in every lifetime. Most wounds heal quickly with little or no attention but, many people suffer from wounds that are complex and/or persistent therefore posing a burden. This study was designed to assess the efficacy of Mitrcarpus villous ointment against honey in diabetic rats. To achieve this, percentage wound closure and collagen assessments were used to express treatment efficacy. Results show that on day 21, rats treated with M. villosus ointment had the highest percentage closure (94.5%) while honey treated and non-treated recorded 90.0% and 83.3% respectively. Similarly, a significant difference (p < 0.05) was observed on day 21 in the total collagen deposited in wounds of diabetic rats (10.57 ± 0.7) and M. villous ointment treated wounds (11.77 ± 0.4) as compared with the non-treated diabetic rats. M. villosus ointment was efficacious in healing wounds in diabetic rats and heals wound faster than honey and may hold potential for wound healing in diabetes mellitus sufferers. However, the wound healing mechanism of this ointment

Keywords: collagen, diabetic rats, honey, Mitracarpus villosus, ointment, wound healing

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Authors: Omolola Soji-Omoniwa, Babasoji Omoniwa

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The hypolipidemic effect of leaf essential oil of Citrus sinensis in alloxan–induced diabetic rats was evaluated. Forty albino rats (150–200 g) were randomly selected into 4 groups of 10 rats each, representing Normal Control, Diabetic Control, Diabetic treated with 14.2 mg/kg body weight Metformin and Diabetic treated with 110 mg/kg body weight leaf essential oil of Citrus sinensis. Diabetes was induced in the animals by intraperitoneal administration of single dose alloxan monohydrate (150 mg/kg body weight). The leaf essential oil of Citrus sinensis was administered every other day to the Diabetic rats for a period of 15 days. The effects of leaf essential oil on High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL), Trigylcerides and Cholesterol were evaluated. A significant reduction (p <0.05) in LDL, Triglycerides and cholesterol levels and a significant increase (p<0 .05) in HDL was observed. Leaf essential oil of Citrus sinensis possesses hypolipidemic properties.

Keywords: Citrus sinensis, Diabetes mellitus, hypolipidemic, leaf essential oil

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Authors: Navpreet Kaur, Randhir Singh

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Diabetic neuropathy is one of the most common microvascular complications of diabetes mellitus which affects more than 50% of diabetic patients. The present study targeted oxidative stress mediated nerve damage in diabetic rats using a hydro-alcohol extract of Cucurbita pepo L. (Family: Cucurbitaceae) and its potential in treatment of diabetic neuropathy. Diabetes neuropathy was induced in Wistar rats by injection of streptozotocin (65 mg/kg, i.p.) 15 min after Nicotinamide (230 mg/kg, i.p.) administration. Hydro-alcohol extract of C. pepo seeds was assessed by oral administration at 100, 200 and 400 mg/kg in STZ-nicotinamide induced diabetic rats. Thermal hyperalgesia (Eddy's hot plate and tail immersion), mechanical hyperalgesia (Randall-Selitto) and tactile allodynia (Von Frey hair tests) were evaluated in all groups of streptozotocin diabetic rats to assess the extent of neuropathy. Tissue (sciatic nerve) antioxidant enzymes (SOD, CAT, GSH and LPO) levels were measured along with the formation of AGEs in serum to assess the effect of hydro-alcohol extract of C. pepo in ameliorating oxidative stress. Diabetic rats exhibited significantly decreased tail-flick latency in the tail-immersion test and decreased paw withdrawal threshold in both Randall-Selitto and von-Frey hair test. A decrease in the nociceptive threshold was accompanied by significantly increased oxidative stress in sciatic nerve of diabetic rats. Treatment with the C. pepo hydro-alcohol extract significantly attenuated all the behavioral and biochemical alterations in a dose-dependent manner. C. pepo attenuated the diabetic condition and also reversed neuropathic pain through modulation of oxidative stress and thus it may find application as a possible therapeutic agent against diabetic neuropathy.

Keywords: advanced glycation end products, antioxidant enzymes, cucurbita pepo, hyperglycemia

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Authors: Md. M. Hossain, Regan Roat, Jenica Christopherson, Colette Free, Zhiguang Guo

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Long noncoding RNA (lncRNA) mediated post-transcriptional gene regulation, and their epigenetic landscapes have been shown to be involved in many human diseases. However, their regulation in diabetes through governing islet’s β-cell function and survival needs to be elucidated. Due to the technical and ethical constraints, it is difficult to study their role in β-cell function and survival in human under in vivo condition. In this study, humanized mice have been developed through transplanting human pancreatic islet under the kidney capsule of NOD.SCID mice and induced β-cell death leading to diabetes condition to study lncRNA mediated regulation. For this, human islets from 3 donors (3000 IEQ, purity > 80%) were transplanted under the kidney capsule of STZ induced diabetic NOD.scid mice. After at least 2 weeks of normoglycecemia, lymphocytes from diabetic NOD mice were adoptively transferred and islet grafts were collected once blood glucose reached > 200 mg/dl. RNA from human donor islets, islet grafts from humanized mice with either adoptive lymphocyte transfer (ALT) or PBS control (CTL) were ribodepleted; barcoded fragment libraries were constructed and sequenced on the Ion Proton sequencer. lncRNA expression in isolated human islets, islet grafts from humanized mice with and without induced β-cell death and their regulation in human islets function in vitro under glucose challenge, cytokine mediated inflammation and induced apoptotic condition were investigated. Out of 3155 detected lncRNAs, 299 that highly expressed in islets were found to be significantly downregulated and 224 upregulated in ALT compared to CTL. Most of these are found to be collocated within 5 kb upstream and 1 kb downstream of 788 up- and 624 down-regulated mRNAs. Genomic Regions Enrichment of Annotations Analysis revealed deregulated and collocated genes are related to pancreas endocrine development; insulin synthesis, processing, and secretion; pancreatitis and diabetes. Many of them, that found to be located within enhancer domains for islet specific gene activity, are associated to the deregulation of known islet/βcell specific transcription factors and genes that are important for β-cell differentiation, identity, and function. RNA sequencing analysis revealed aberrant lncRNA expression which is associated to the deregulated mRNAs in β-cell function as well as in molecular pathways related to diabetes. A distinct set of candidate lncRNA isoforms were identified as highly enriched and specific to human islets, which are deregulated in human islets from donors with different BMIs and with type 2 diabetes. These RNAs show an interesting regulation in cultured human islets under glucose stimulation and with induced β-cell death by cytokines. Aberrant expression of these lncRNAs was detected in the exosomes from the media of islets cultured with cytokines. Results of this study suggest that the islet specific lncRNAs are deregulated in human islet with β-cell death, hence important in diabetes. These lncRNAs might be important for human β-cell function and survival thus could be used as biomarkers and novel therapeutic targets for diabetes.

Keywords: β-cell, humanized mouse, pancreatic islet, LncRNAs

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Authors: Shiva Emami, Jenny Persson, Bengt Johansson Lindbom

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Group A streptococcus (GAS) is a prevalent human pathogen, causing a wide range of infections and diseases. One of the most well-known virulence factors in GAS is M protein, a surface protein that facilitates bacterial invasion. In this study, we used a recombinant GAS strain (GAS-2W) expressing M protein containing a hyper immunogenic peptide (2W). Mice were immunized three times with heat-killed-GAS subcutaneously at three weeks intervals. Three weeks post last immunization, mice were challenged intraperitoneally with a lethal dose of live GAS. In order to investigate the impact of IFN-ƴ and antibodies in protection against GAS infection, we used a mouse model knock-out for IFN-ƴ (IFN-ƴ KO). We observed immunization with GAS-2W strain can increase protection against GAS infection in mice compared with the original GAS strain. Higher levels of antibodies against M1 protein were measured in GAS-2W-immunized mice. There was also a significant increase in IgG2c response in mice immunized with GAS2W. By using IFN-ƴ KO mice, we showed that not a high level of total IgG, but IgG2c was correlated with protection through the i.p challenge. It also emphasizes the importance of IFN-ƴ cytokine to combat GAS by isotype switching to IgG2c (which is opsonic for phagocytosis). Our data indicate the crucial role of IFN-ƴ in the protective immune response that, together with IgG2c, can induce protection against GAS.

Keywords: Group A streptococcus, IgG2c, IFN-γ, protection

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Authors: Smita Shenoy, Amoolya Gowda, Tara Shanbhag, Krishnananda Prabhu, Venumadhav Nelluri

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The study was undertaken to assess the effect of ethanolic extract of Michelia champaca on excision wound healing in diabetic wistar rats. Excision wound was made in five groups of rats after inducing diabetes with streptozotocin in four groups. Paraffin was applied to wounds in nondiabetic and diabetic control and 2.5%, 5%, 10% ointment of extract to wounds in three diabetic test groups. Monitoring of wound contraction rate, the period of epithelization and histopathological examination of granulation tissue was done. There was a significant (p < 0.05) decrease in the period of epithelization and a significant increase in the wound contraction rate on day 12 and 16 in rats treated with 5% and 10% ointment as compared to diabetic rats. There was a better organization of collagen fibers in the granulation tissue of wounds treated with 10% ointment. The higher dose of ethanolic extract of Michelia champaca promoted wound healing in diabetic Wistar rats.

Keywords: Michelia champaca, excision wound, contraction, epithelization

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Authors: P. O. Ughachukwu, P. O. Okonkwo, P. C. Unekwe, J. O. Ogamba

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Background: The prevalence of hepatitis B viral infection is high worldwide with liver cirrhosis and hepatocellular carcinoma as important complications. Cases of poor antibody response to hepatitis B vaccination abound. Immunosuppression, especially from glucocorticoids, is often cited as a cause of poor antibody response and there are documented evidences of irrational administration of glucocorticoids to children and adults. The study was, therefore, designed to find out if administration of glucocorticoids affects immune response to vaccination against hepatitis B in mice. Methods: Mice of both sexes were randomly divided into 2 groups. Daily intramuscular methylprednisolone injections, (15 mg kg-1), were given to the test group while sterile deionized water (0.1ml) was given to control mice for 30 days. On day 6 all mice were given 2 μg (0.1ml) hepatitis B vaccine and a booster dose on day 27. On day 34, blood samples were collected and analyzed for anti-HBs titres using enzyme-linked immunosorbent assay (ELISA). Statistical analysis was done using Graph Pad Prism 5.0 and the results taken as statistically significant at p value < 0.05. Results: There were positive serum anti-HBs responses in all mice groups but the differences in titres were not statistically significant. Conclusions: At the dosages and length of exposure used in this study, methylprednisolone injection did not significantly inhibit anti-HBs response in mice following immunization against hepatitis B virus. By extrapolation, methylprednisolone, when used in the usual clinical doses and duration of therapy, is not likely to inhibit immune response to hepatitis B vaccinations in man.

Keywords: anti-HBs, hepatitis B vaccine, immune response, methylprednisolone, mice

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Authors: Rubaiyea Uddin

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The hippocampus, located in the limbic system, is most commonly known for its role in memory and spatial navigation (as cited in Brain Reward and Pathways). It maintains an especially important role in specifically episodic and declarative memory. The hippocampus has also recently been linked to dopamine, the reward pathway’s primary neurotransmitter. Since research has found that dopamine also contributes to memory consolidation and hippocampal plasticity, this neurotransmitter is potentially responsible for contributing to the hippocampus’s role in memory formation. In this experiment we tested to see the effect of tactile cues on spatial navigation for eight different mice. We used a radial arm that had one designated 'reward' arm containing sucrose. The presence or absence of bedding was our tactile cue. We attempted to see if the memory of that cue would enhance the mice’s memory of having received the reward in that arm. The results from our study showed there was no significant response from the use of tactile cues on spatial navigation on our 129 mice. Tactile cues therefore do not influence spatial navigation.

Keywords: mice, radial arm maze, memory, spatial navigation, tactile cues, hippocampus, reward, sensory skills, Alzheimer’s, neurodegnerative disease

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Authors: Hanjun Zhao

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Limited efficacy of current antivirals and antiviral-resistant mutations impair anti-influenza treatment. Here, we evaluated the in vitro and in vivo antiviral effect of three defective interfering genes (DIG-3) of influenza virus. Virus replication was significantly reduced in 293T and A549 cells transfected with DIG-3. Mice transfected with DIG-3 encoded by jetPEI-vector, as prophylaxis and therapeutics against A(H7N7) virus respectively, had significantly better survivals (80% and 50%) than control mice (0%). We further developed a dual-functional peptide TAT-P1, which delivers DIG-3 with high transfection efficiency and concomitantly exerts antiviral activity by preventing endosomal acidification. TAT-P1/DIG-3 was more effective than jetPEI/DIG-3 in treating A(H7N7) or A(H1N1)pdm09-infected mice and showed potent prophylactic protection on A(H7N7) or A(H1N1)pdm09-infected mice. The addition of P1 peptide, preventing endosomal acidification, could enhance the protection of TAT-P1/DIG-3 on A(H1N1)pdm09-infected mice. Dual-functional TAT-P1 with DIG-3 can effectively protect or treat mice infected by avian and seasonal influenza virus infection.

Keywords: antiviral peptide, dual-functional peptide, defective interfering genes, influenza virus

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Authors: F. Motamedi Sedeh, Sh. Chahardoli, H. Mahravani, N. Harzandi, M. Sotoodeh, S. K. Shafaei

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Foot-and-mouth disease virus (FMDV) is the most economically important disease of livestock. The aim of the study is inactivation of FMD virus type O/IRN/2010 by electron beam without antigenic changes as electron radio vaccine. The BALB/C mice were divided into three groups, each group containing five mice. Three groups of mice were inoculated with conventional vaccine and electron beam irradiated vaccine FMDV type O/IRN/2010 subcutaneously three weeks interval, the final group as negative control. The sera were separated from the blood samples of mice 14 days after last vaccination and tested for the presence of antibodies against FMDV type O/IRN/2010 by serum neutralization test. The Serum Neutralization Test (SNT) was carried out and antibody titration was calculated according to the Kraber protocol. The results of the SNT in three groups of mice showed the titration of neutralizing antibody in the vaccinated mice groups; electron radio vaccine and conventional vaccine were significantly higher than negative control group (P<0.05). Therefore, the radio vaccine is a good candidate to immunize animals against FMDV type O/IRN/2010.

Keywords: FMDV type O/IRN/2010, neutralizing antibody response, electron beam, radio vaccine

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Authors: Nurul Z. Sani, Amalina N. Ghazali, Azree Elmy, Lee C. Yuen, Zar C. Thent

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Piper betel (P. betel) leaves is widely used in Asian countries for treating diabetes mellitus and its complication. In our previous study, we observed the positive effect of P.betel extract on diabetic wounds following 3 and 7 days of treatment. The aim of the present study was to determine the effect of P.betel leaves extract in the diabetic rats was observed in terms of body weight and wound contraction rates following 5 days of the treatment. Total 64 male Sprague-Dawley rats were used and the experimental rats received a single dose of 60mg/kg of Streptozotocin (STZ) injection, intraperitoneally. Four full thickness (6mm) cutaneous wounds were created on dorsum of each rat. The rats were divideid into (n=8): Non-treated Control (NC), Non-treated Diabetic (ND), diabetic treated with commercial cream (SN) and diabetic treated with 50mg/kg of P.betel extract (PB). The rats were sacrificed on day 0 and 5 post wounding. Significant increased in wound closure rate, body weight was observed in PB group compared to ND. Histological deterioration was restored in the P. betel extract treated wounds. It is concluded that topical application with P.betel extract for 5 days of post wounding offers positive scientific value in diabetic rats.

Keywords: diabetes, piper betel, wound healing, body weight, morphology

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Authors: Xing Wang, Lin Feng, Lingling E., Hongchen Liu

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In patients with type 2 diabetes mellitus (DM) there is poorer quality osseointegration than in non-diabetic (n-DM) patients, and the success of dental implants is less. Recent studies have demonstrated that insulin could stimulate bone cells to produce and accelerate implant osseointegration in DM patients.This raised the question whether insulin could provide local bone anabolic effects in non-diabetic patients. In this study,48 SD rats were divided into four groups randomly: DM group, DM+insulin group, n-DM group, n-DM + insulin group. All rats were implanted the titanium implant near the epiphyseal end of tibia, then the DM + insulin and n-DM + insulin group received twice-daily subcutaneous injections of insulin (10U/day).Two,four and eight weeks after implantation, rats were killed in batches. Histomorphometry and immunohistochemistry were used to evaluate bone formation and osseointegration. The amount of newly formed bone, Implant–bone contact and the expression of OCN,RUNX2 in the DM+insulin, n-DM and n-DM+insulin group were significantly more than in the DM group (p<0.05). Compared with the n-DM group,the Implant–bone contact and expression of OCN,RUNX2 were significantly increased in n-DM+insulin group (p< 0.05). Taken together,these observations provide evidence that insulin has the potential to increase bone formation and osseointegration around implant not only in diabetic subjects but also in non-diabetic subject.

Keywords: insulin, diabetes mellitus, osseointegration, dental implants

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Authors: Maha Deif, Alaa Eldin Hassan, Eman Shaat, Nesrine Elazhary, Eman Magdy

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Background: Erythropoietin (EPO) is a hematopoietic factor with multiple protective effects. The aim of the present study was to investigate the potential effect of EPO administration on renal functions and hypoxia inducible factor 1-alpha (HIF-1a) in diabetic rat kidneys. Methodology: The current study was carried out on 40 male albino rats divided into four groups (n= 10 in each). Group I served as normal control, group II was the diabetic control, group III rats received EPO on the same day of diagnosis of diabetes mellitus (DM), while group IV received the first dose of EPO 2 weeks after the diagnosis of DM. Results: The results showed that EPO supplementation leads to a significant decrease in serum urea, urinary protein and creatinine clearance as well as a significant increase in renal HIF-1a in group III and IV rats compared to the diabetic control group (group II). However, fasting blood glucose was significantly decreased in group III as compared to the diabetic control group in the third week, but no significant difference was reported in the fourth week among groups II, III and IV. Conclusion: EPO administration leads to the improvement of renal functions and increased levels of HIF-1a in diabetic rats.

Keywords: erythropoietin, diabetic nephropathy, hypoxia-inducible factor1-alpha, renal functions

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Authors: A. Bhattacharya, Sanjay Gupta, S. H. Bodakhe

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HbA1c is form of the haemoglobin that is used to measure the average plasma glucose concentration over prolonged periods of time. It is formed in a non-enzymatic glycation pathway by hemoglobin's exposure to plasma glucose. In diabetes mellitus, higher amounts of glycated hemoglobin, indicating poorer control of blood glucose levels, have been associated with cardiovascular disease, nephropathy, and retinopathy. Guraku’s basic components are nicotine and jaggery, jaggery is made up of sugarcane so can have a diabetogenic potential which is exacerbated in presence of nicotine. This work had done with the aim to find correlation between Diabetic cataract, HbA1c and Guraku. Subjects were enrolled according to the inclusion and exclusion criteria. In this study total 75 subjects were included. In the study it was found that people consuming Guraku had a high level of HbA1c thus are more prone to the development of diabetic cataract. Male subjects are the more than female subjects. Most of the subjects belong to the lower socioeconomical class and not very educated. It could be concluded that this type of study could be useful in indentifying number of subjects suffering from diabetic cataract whose condition get worse by use of nicotine product like Guraku and preventive measure to be taken in prevention of this type of diabetic complication.

Keywords: diabetic cataract, HbA1c, Guraku, diabetogenic potential

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Authors: Vishnu Varthan Vaithiyalingamjagannathan, M. N. Sathishkumar, K. S. Lakhsmi, D. Satheeshkumar, Srividyaammayappanrajam

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Background:Naringenin, aglycone flavonoid possess certain activities like anti-oxidant, anti-estrogenic, anti-diabetic, cardioprotective, anti-obesity,anti-inflammatory, hepatoprotective and also have anti-cancer characteristics like carcinogenic inactivation, cell cycle arrest, anti-proliferation, apoptosis, anti-angiogenesis and enhances anti-oxidant activity. Methodology:The inhibitory effect of Naringenin in lung tumor progression estimated with adenocarcinoma (A549) cell lines (in vitro) and C57BL/6 mice injected with 5 X 106A549 cell lines (in vivo) in a tri-dose manner (Naringenin 100mg/kg,150mg/kg, and 200mg/kg) compared with standard chemotherapy drug cisplatin (7mg/kg). Results:The results of the present study revealed a dose-dependent activity in Naringenin and combination with cisplatin at a higher dose which showed decreased tumor progression in mice. In vitro studies carried out for estimation of cell survival and Nitric Oxide (NO) level, shows dose dependent action of Naringenin with IC50 value of 42µg/ml. In vivo studies were carried out in C57BL/6 mice. Naringenin satisfied the condition of an anti-cancer molecule with its characteristics in fragmentation assay, Zymography assay, anti-oxidant, and myeloperoxidase studies, than cisplatin which failed in anti-oxidant and myeloperoxidase effect. Both in vitro and in vivo establishes dose dependent decrease in NO levels. But whereas, Naringenin showed adverse results in Matrix Metalloproteinase (MMP) enzymatic levels with increase in dose levels. Conclusion:From the present study, Naringenin could suppress the lung tumor progression when given individually and also in combinatorial with standard chemotherapy drug.

Keywords: naringenin, in vitro, cell line, anticancer

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Authors: Lívia Pimentel Sant'ana Dourado, Raquel Das Neves Almeida, Luís Henrique Costa Corrêa Neto, Nayara Soares, Kelly Grace Magalhães

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Introduction: Obesity and high-fat diet intake have a crucial impact on immune cells and inflammatory profile, highlighting an emerging realization that obesity is an inflammatory disease. In the present work, we aimed to characterize the role of caspase-1/11 and NLRP3 inflammasome in the establishment of mice obesity and modulation of inflammatory lipid metabolism induced by high fat diet intake. Methods and results: Wild type, caspase-1/11 and NLRP3 knockout mice were fed with standard fat diet (SFD) or high fat diet (HFD) for 90 days. The weight of animals was measured weekly to monitor the weight gain. After 90 days, the blood, peritoneal lavage cells, heart and liver were collected from mice studied here. Cytokines were measured in serum by ELISA and analyzed in spectrophotometry. Lipid antigen presentation molecule CD1d expression, reactive oxygen species (ROS) generation and lipid droplets biogenesis were analyzed in cells from mice peritoneal cavity by flow cytometry. Liver histopathology was performed for morphological evaluation of the organ. The absence of caspase-1/11, but not NLRP3, in mice fed with HFD favored the mice weight gain, increased liver size, induced development of hepatic steatosis and IL-12 secretion in mice compared to mice fed with SFD. In addition, caspase-1/11 knockout mice fed with HFD presented an increased CD1d molecule expression, as well as higher levels of lipid droplets biogenesis and ROS generation compared to wild type mice also fed with HFD. Conclusion: Our data suggest that caspase-1/11 knockout mice have greater susceptibility to obesity as well as increased activation of lipid metabolism and inflammatory markers.

Keywords: caspase 1, caspase 11, inflamassome, obesity, lipids

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Authors: P. Akbartehrani, M. Khaledi Pour, M. Amini, M. Khani, M. Mohajeri Tehrani, E. Ghasemi, P. Charipoor, B. Shokri

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A common problem between diabetic patients is foot ulcers which are chronic and require specialized treatment. Previous studies illustrate that Cold atmospheric plasma (CAP) has beneficial effects on wound healing and infection. Nevertheless, the comparison of different cap exposure protocols in diabetic ulcer wound healing remained to be studied. This study aims to determine the effect of two different exposure protocols on wound healing in diabetic ulcers. A prospective, randomized clinical trial was conducted at two clinics. Diabetic patients with G1 and G2 wanger classification diabetic foot ulcers were divided into two groups of study. One group was treated by the first protocol, which was treating wounds by argon-generated cold atmospheric plasma jet once a week for five weeks in a row. The other group was treated by the second protocol, which was treating wounds every three days for five weeks in a row. The wounds were treated for 40 seconds/cubic centimeter, while the nozzle tip was moved nonlocalized 1 cm above the wounds. A patient with one or more wounds could participate in different groups as wounds were separately randomized, which allow a participant to be treated several times during the study. The study's significant findings were two different reductions rate in wound size, microbial load, and two different healing speeds. This study concludes that CAP therapy by the second protocol yields more effective healing speeds, reduction in wound sizes, and microbial loads of foot ulcers in diabetic patients.

Keywords: wound healing, diabetic ulcers, cold atmospheric plasma, cold argon jet

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Authors: Amina Bouzitouna, Kheireddine Ouali, Sandra Amri, Houria Rahmoun, Mourad Bensouilah

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Aim of this study: To evaluate the effect of Cisthanche tinctoria treatment on maternal-fetal outcome and antioxidant systems of streptozotocin-induced diabetic rats. Materials and methods: Virgin female Wistar rats were injected with 50 mg/kg streptozotocin before mating. Oral administration of an methanolic extract of Cistanche tinctoria was given to non-diabetic and diabetic pregnant rats at doses of 200 mg/kg from 0 to 19th day of pregnancy. At day 20 of pregnancy the rats were killed and a maternal blood sample was collected for the determination Vitamin C (Vit C) and malonaldehyde (MDA). The gravid uterus was weighed with its contents and fetuses were analyzed. Results and conclusion: The data showed that the diabetic dams presented an increased glycemic level, resorption, placental weight, placental index, and fetal anomalies, and reduced VIT C and MDA determinations, live fetuses, maternal weight gain, gravid uterine weight, and fetal weight. It was also verified that Cisthanche tictoria treatment had no hypoglycemic effect, did not improve maternal outcomes in diabetic rats, but it contributed to maintain GSH concentration similarly to non-diabetic groups, suggesting relation with the decreased incidence of visceral anomalies.

Keywords: cistanche tinctoria, diabetes, pregnancy, reproductive outcome, anomaly, orobanchacées

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Authors: Mhuji Kilonzo

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Acute oral toxicity of Mystroxylon aethiopicum root bark aqueous was evaluated in albino mice of either sex. In this study, five groups of mice were orally treated with doses of 1000, 2000, 3000, 4000 and 5000 mg/kg body weight of the crude extract. The mortality, signs of toxicity and body weights were observed individually for two weeks. At the end of the two weeks study, all animals were sacrificed, and the hematological and biochemical parameters, as well as organ weights relative to body weight of each animal, were determined. No mortality, signs of toxicity and abnormalities in vital organs were observed in the entire period of study for both treated and control groups of mice. Additionally, there were no significant changes (p > 0.05) in the blood hematology and biochemical analysis. However, the body weights of all mice increased significantly. The Mystroxylon aethiopicum root bark aqueous extract were found to have a high safe margin when administered orally. Hence, the extract can be utilized for pharmaceutical formulations.

Keywords: acute oral toxicity, albino mice, Mystroxylon aethiopicum, safety

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Authors: Alia Ali, Azeem Taj, Muhammed Joher Amin, Farrukh Iqbal, Zafar Iqbal

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Background: Hypertension is commonly found in patients with Diabetic Kidney Disease (DKD). Microalbuminuria is the first clinical sign of involvement of kidneys in patients with type 2 diabetes. Uncontrolled hypertension induces a higher risk of cardiovascular events, including death, increasing proteinuria and progression to kidney disease. Objectives: To determine the correlation between microalbuminuria and hypertension and their association with other risk factors in type 2 diabetic patients. Methods: One hundred and thirteen type 2 diabetic patients were screened for microalbuminuria and raised blood pressure, attending the diabetic clinic of Shaikh Zayed Hospital, Lahore, Pakistan. The study was conducted from November 2012 to June 2013. Results: Patients were divided into two groups. Group 1, those with normoalbuminuria (n=63) and Group 2, those having microalbuminuria (n=50). Group 2 patients showed higher blood pressure values as compared to Group 1. The results were statistically significant and showed poor glycemic control as a contributing risk factor. Conclusion: The study concluded that there is high frequency of hypertension among type 2 diabetics but still much higher among those having microalbuminuria. So, early recognition of renal dysfunction through detection of microalbuminuria and to start treatment without any delay will confer future protection from end-stage renal disease as well as hypertension and its complications in type 2 diabetic patients.

Keywords: hypertension, microalbuminuria, diabetic kidney disease, type 2 Diabetes mellitus

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