Search results for: serum miRNA

Authors: Ramalingam Boobalan, Chinpiao Chen, Jui-I. Chiao

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A series of erlotinib analogues that have structural modification at 6,7-alkoxyl positions is efficiently synthesized. The key reactions that involved in synthesis are one-pot oxime formation-dehydration for the formation of nitrile, quinazoline ring formation reaction between aniline and o-cyanoaniline via formamidine intermediate, Fe/NH4Cl catalyzed reduction-hetereocyclization-reductive ring opening reaction for the formation of o-aminobenzamide, high yielding seal tube reactions for O-demethylation, sodium iodide substitution, ammonia substitution. The in vitro anti-tumor activity of synthesized compounds is studied in two non-small cell lung cancer (NSCLC) cell lines (A549 and H1975). Among the synthesized compounds, the iodo compound 6 (ETN-6) exhibits higher anti-cancer activity compared to erlotinib. An efficient method is developed for the conjugation of erlotinib analogue-4, alcohol compound, with protein, bovine serum albumin (BSA), via succinic acid linker. The in vitro anti-tumor activity of the protein attached erlotinib analogue, 8 (ETN-4-Suc-BSA), showed stronger inhibitory activity in both A549 and H1975 NSCLC cell lines.

Keywords: anti-cancer, BSA, EGFR, Erlotinib

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Authors: Bidya Dhar Sahu, Meghana Koneru, R. Shyam Sunder, Ramakrishna Sistla

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Environmental and occupational exposure to hexavalent chromium [Cr(VI)] via textile manufacture, metallurgy, spray paints, stainless steel industries, drinking water containing chromium are often known to cause acute renal injury in humans and animals. Nephrotoxicity is the major effect of chromium poisoning. In the present study, we investigated the potential renoprotective effect and underlying mechanisms of carvedilol using rat model of potassium dichromate (K2Cr2O7)-induced nephrotoxicity. Exploration of the underlying mechanisms of carvedilol revealed that carvedilol attenuated nuclear translocation and DNA binding activity of NF-κB (p65), restored antioxidant and mitochondrial respiratory enzyme activities and attenuated apoptosis related protein expressions in kidney tissues. The serum levels of TNF-α, the renal iNOS and myeloperoxidase activity were significantly decreased in carvedilol pre-treated K2Cr2O7-induced nephrotoxic rats. These results were further supported and confirmed by histological findings. In conclusion, the findings of the present study demonstrated that carvedilol is an effective chemoprotectant against K2Cr2O7-induced nephrotoxicity in rats.

Keywords: apoptosis, carvedilol, inflammation, potassium dichromate-induced nephrotoxicity, applied pharmacology

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Authors: Ali Olfati, Parichehr Nouri

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Objective: In this study, we have investigated for the first time in the literature the efficacy of riboflavin [VB2] in preventing uterus As₂O₃ damage. Methods: Rats received 40 μg LHRHa for estrus synchronization. 48 pregnant Wistar rats were included. Four groups were formed with 7 rats in each group: Sham, 1.5 mg arsenic trioxide (As₂O₃/L) alone or in combination with VB2 [20 and 40 mg/L] in drinking water [for 21 days continuously]. Similar to maternal generation treatment, the F1-female generation was also arranged [for 35 days continuously until puberty]. Results: Data indicated that As₂O₃ reduced body weight and feed intake (p<0.05). Furthermore, the serum malondialdehyde levels in the As₂O₃ group were significantly higher than that of the control group (p<0.05). At the same time, total antioxidative status and the activities of glutathione peroxidase, superoxide dismutase, and catalase were reduced (p<0.05). Meanwhile, As₂O₃ remarkably increased the production of inflammatory markers [interleukin 6 and C-reactive protein](p<0.05). As₂O₃ administration induced uterus apoptosis-related genes by upregulating caspase-3, iNOS, and Bax genes and downregulating Bcl-2 gene of pubertal F1-female rats (p<0.05). Conclusion: Our observation indicated that VB2 therapy is potentially an effective strategy to modifying the detrimental effects of As₂O₃ in pubertal F1-female rats via suppresses oxidative damages.

Keywords: As₂O₃, inflammation, puberty, vitamin B2

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Authors: Lai Tzu-Hsuan, Lai Jung-Nien, Lin Jaung-Geng, Kao Shung-Te, Hsuan-Kuang Jung

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Background: Whether acupuncture therapy contributes to preserving residual renal function (RRF) remains largely unknown. This case series evidenced the potential beneficial effects of acupuncture for preserving RRF in five patients with the end-stage renal disease under hemodialysis (HD) treatment. Participants: Five patients on HD receiving eight sessions of weekly 30-min interdialytic acupuncture (Inter-A) with residual urine volume (rUV) and residual glomerular filtration rate (rGFR) recorded once every two weeks were included for analysis. Outcomes: Changes in rUV and rGFR calculated using 24-hour urine collection data were analyzed to assess RRF. Variations in hemoglobin, urea Kt/V and serum albumin levels measured monthly were analyzed to evaluate HD adequacy. Results: After eight Inter-A sessions, mean (standard deviation (SD)) rUV and rGFR increased from 612 (184) ml/day and 1.48 (.94) ml/min/1.73 m2 at baseline to 803(289) ml/day and 2.04(1.17) ml/min/1.73m2 at 2- and 4-week follow-up, respectively. The mean percentage difference increased by 31% in rUV and 38% in rGFR. Routine measurements on HD adequacy also showed improvement. Conclusions: Acupuncture might be an optional add-on treatment for HD population with poor control of water; however, further well-designed controlled trials are warranted.

Keywords: end-stage renal disease, hemodialysis, acupuncture, residual renal function, residual urine volume

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Authors: Y. A. Shettima, M. A. Tijjani, S. Modu, F. I. Abdulrahman, B. M. Abubakar

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The toxicity profile of the methanolic extract of Punica granatum L. fruit rind was studied in normal rats. The rats were administered orally by intubating graded doses of 150, 250, 500 and 750 mg/kg body weight of the extract for 28 days and the effects on biochemical parameters and histology of the liver and kidney were evaluated. There was a significant increase (P<0.05) in the levels of liver enzymes of the rats that received the highest dose of 750 mg/kg body weight. The AST and ALT levels were 41.59±0.18 ALP and 9.25±0.29 IU/L, respectively, while the ALP level was 15.68±10 IU/L.There was a significant difference in the albumin and globulin levels; 3.72±0.05 and 4.05±0.13 g/dl, respectively. Serum urea and creatinine levels remained normal, as well as the electrolyte levels. The increase in sodium concentration observed was not statistically significant (P≥0.05) when the control group (131.50±3.11) was compared with the experimental groups (132.25±3.86, 132.75±3.86, 133.50±3.11 and 134.00±1.83). The increase in potassium concentration was not statistically significant (P≥0.05) when the control group with a value of 95.50±3.51 mmol/L was compared with the experimental groups 98.00±3.16, 99.25±2.22, 99.79±0.36 and 99.99±0.02 mmol/L. The increase observed in bicarbonate concentration was not statistically significant (P≥0.05) when the control group with a value of 20.75±1.71 mmol/L was compared with the experimental groups 21.68±0.62, 24.25±2.99, 24.50±3.42, 25.50±2.65 mmol/L.

Keywords: punical granatum, methanolic, ALT, AST, electrolytes, histology

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Authors: Nasib Zaman, Maneesha Kour, Muhammad Rizwan, Fazal Akbar

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Abstract: Chikungunya fever is a re-emerging rapidly spreading mosquito-borne disease cause by Aedes albopictus and Aedes aegypti mosquito vectors. Currently, it is affecting millions of people globally. Objective: This study's main objective was to find the incidence of chikungunya fever in the Swat region and the factors associated with the spread of this infection. Method: This study was carried out in different areas of Swat. Blood samples and data were collected from selected patients, and a questionnaire was filled for each patient. 3-5ml of the specimen was taken from the patient's vein and serum, or plasma was separated by centrifugation. Chikungunya tests were performed for IgG and IgM antibodies. The data was analyzed by SPSS and Graph Paid Prism 5. Results: A total of 169 patients were included in this study, out of which 103 (60.9%) having age less than 30 years were positive for chikungunya infection and 66 (39.1%) having more than 30 years were negative for this infection. Only 1 (0.6%) were positive for both IgG and IgM antibody. About 15 (8.9%) patients have diagnosed with positive IgG antibodies, and 25 (26.6%) patients were positive for IgM positive antibodies. The infection rate was significantly higher in males compared to females 71 (59.6%) vs. 14 (38%) P value=0.088, OR=1.7. Conclusion: This study concludes clinical knowledge and awareness that are necessary for a diagnosis of chikungunya infection properly. Therefore it is important to educate people for the eradication of this infection. Recommendation: This study also recommends investigating the other risk factors associated with this infection.

Keywords: Chikungunya, risk factor, Incidence, antibodies, mosquito

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Authors: Fateme Afkhami, Mohsen Ehsanpour, Majid Afkhami, Maryam Ehsanpour

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Normal reference ranges of biochemical parameters are considered important for assessing and monitoring the health status of sea turtles. For this means, serum biochemistry determinations were analyzed in normal adult nesting and foraging hawksbill turtles (Eretmochelys imbricata). Blood samples were collected in March–April during nesting season and December-November in the foraging season. Plasma biochemistry values, except for creatinine and lipase were significant between the two periods. FBS, cholesterol, triglycerides, ALP (alkaline phosphatase), AST (aspartate aminotransferase), bilirubin, total protein, LDH (lactate dehydrogenase), CK (creatine kinase) and amylase were significantly higher in nesting season than foraging season (P<0.05). On the other hand urea, ALT (alanine aminotransferase) and albumin in the nesting season were significantly lower than foraging season (P<0.05). It was concluded that the nesting E. imbricata showed significant variation in their biochemical profile due to reproductive output. This study has produced working reference intervals useful for hawksbill turtles for future conservation and rehabilitation projects in the Persian Gulf and may be of assistance in similar programs worldwide.

Keywords: plasma biochemistry, nesting, foraging, hawksbill turtles, Persian Gulf

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Authors: Dara Kutsyk, Olga Bondarenko, Mariya Sorochka

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In 21-century type 2 diabetes (T2D) has become a global health and social problem in the whole world. The goal of treatment for patients with T2D is to prevent complications of diabetes - macrovascular diseases (heart disease, stroke, and peripheral vascular disease) and microvascular diseases (retinopathy, neuropathy and nephropathy). Nitric oxide (NO) plays an important role in maintaining vascular homeostasis. Loss of NO function is one of the earliest indicators of disease and its progression especially in patients with T2D. Aim: To compare NO level between patients with well and bad controlled glycemia in T2D. Methods: The study included 32 patients with T2D. The diagnosis of T2D was confirmed due to International Diabetes Federation (IDF) criteria 2015. Patients were divided into two groups: with well controlled glycaemia (HbA1c < 7%) and bad controlled glycaemia (HbA1c > 7%). The control group consists of 15 healthy subjects. Results: NO level in patients with T2D is significantly higher (27,2 ±3,1 µmol), compared to controls (18,86±0,9 µmol; p < 0,001). A significant difference in NO level was found between patients with bad controlled glycaemia (25,9±2,2 µmol) and well controlled glycaemia (28,7 ± 3,0 µmol; p<0,01). The study showed a moderate negative correlation between NO level and HbA1c (-0,399; р< 0,05). Conclusions: Production of NO is impaired in patients with T2D, especially with badly controlled glycaemia. With the increase in HbAc serum NO decreases. This can be the main target for prevention vascular complication in T2D.

Keywords: type 2 diabetes, glycated hemoglobin, nitric oxide, Diabetes mellitus

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Authors: Farah Nameni, Hamidreza Poursadra, Maasumeh Nurani Pilehrud

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Exercise training induced Inflammation and stress. Antioxidant, for example L- Carnitine has beneficial effects in immune system and increased antioxidant enzymes activity. L- Carnitine protects the tissue against the oxidative side effect and helps the body to protect against stress during and after acute exercise. The aim of this study was to determine the effect of L-Carnitine on the blood enzymes: GPX SOD, CAT and GR response. In this study, 20 basketball players girls participated. Subjects were randomly assigned into two groups; placebo and supplementation. Antioxidadision enzymes (Superoxide Dismutase, Catalase, Glutathione Reductase, Glutathione Peroxidase) evaluated. L-Carnitine supplement group orally daily received 3000 mg powder for 14 dys. Then all participates trained basketball exercise acute. Blood samples were drawn vein before and immediately after exercise. Superoxide Dismutase, Catalase, Glutathione Reductase, Glutathione Peroxidase were measured, and data was analyzed using repeated measure ANOVA, Bonferroni and t-test. Our results showed: SOD, GPX and GPX (P < 0.05) have a significant increase. These results suggest L-Carnitine supplementation may increase GPX SOD, CAT, and basal anti oxidative capacity. L-Carnitine can modulate the alterations of exercise oxidative damage in girl basketball players.

Keywords: l-carnitine, GPX, SOD, CAT, exercise, GR, anti-oxidant

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Authors: Riddhi Trivedi, Shrenik Shah

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For Si RNA to be delivered various biodegradable polymers are trialed by many researchers. One of them is Chitosan (CS) nanoparticles which have been extensively studied for siRNA delivery but the stability and efficacy of such particles are highly dependent on the types of cross-linker used. Hence the attempts are made in this study with PGA To address this issue, three common cross-linkers; Ethylene glycol diacrylate (ED) and poly-D-glutamic acid (PGA) were used to prepare siRNA loaded CS-ED/PGA nanoparticles by ionic gelation method. The nanoparticles which were obtained were compared for its characterization in terms of its physicochemical properties i.e. particle size of the resultant particles, zeta potential, its encapsulation capacity in the polymer. Among all the formulations prepared with different crosslinker PGA siRNA had the smallest particle size (ranged from 120 ± 1.7 to 500 ± 10.9 nm) with zeta potential ranged from 22.1 ± 1.5 to +32.4 ± 0.5 mV, and high entrapment ( > 91%) and binding efficiencies. Similarly, CS-ED nanoparticles showed better siRNA protection during storage at 4˚C and as determined by serum protection assay. TEM micrographs revealed the assorted morphology of CS-PGA-siRNA nanoparticles in contrast to irregular morphology displayed by CS-ED-siRNA. All siRNA loaded nanoparticles were found to give initial burst release which after some time followed by a sustained release of siRNA which were loaded inside. All the formulations showed concentration-dependent cytotoxicity with when cytotoxicity performed by HeLa and normal vero cell lines.

Keywords: chitosan, siRNA, cytotoxicity, cell line study

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Authors: Maria Angelica Trak-Fellermeier, Alison K. Macchi, Rodolfo Galvan, Yolangel Hernandez, Thresia Gambon, Rebeca Martinez, Cristina Palacios

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Poor lifestyle habits, vitamin D deficiency, and inadequate calcium intake, particularly during the COVID-19 pandemic, may contribute to severe osteopenia in childhood, increasing future fractures and osteoporosis risk. We here present a case of osteopenia in a 13-year-old white, Hispanic, premenarchal girl who completed the baseline visit of the MetA-Bone Trial during the COVID-19 pandemic. The premenarchal girl has a family history of osteoporosis (maternal grandfather) but no previous fractures; moderate outdoor activity was <1 hour/day 3 times/week with 8 hours/day of sleep. Consumption of dairy products and vegetables was <1 serving/day. Lab blood tests confirmed vitamin D deficiency (serum 25(OH)D: 9 ng/L) and hyperphosphatemia (5.2 mg/dL); other tests were normal. DXA scan Z‐score was ‐2.2 SD (indicative of osteopenia by age and sex). The premenarchal girl was referred to a pediatrician, who confirmed the results, and prescribed a daily supplement with 2000 IU of vitamin D and 1000 mg of calcium. Seclusion during the COVID-19 pandemic may have contributed to the severity of the findings. Therefore, we recommend screening children undergoing growth spurts for vitamin D, calcium, and poor lifestyle habits during and after the pandemic.

Keywords: bone mass, vitamin D, puberty, Hispanic

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Authors: Adela Diepoltova, Klara Konecna, Ondrej Jandourek, Petr Nachtigal

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A loss of control over antibiotic-resistant pathogens has become a global issue due to severe and often untreatable infections. This state is reflected in complicated treatment, health costs, and higher mortality. All these factors emphasize the urgent need for the discovery and development of new anti-infectives. One of the most common pathogens mentioned in the phenomenon of antibiotic resistance are bacteria of the genus Staphylococcus. These bacterial agents have developed several mechanisms against the effect of antibiotics. One of them is biofilm formation. In staphylococci, biofilms are associated with infections such as endocarditis, osteomyelitis, catheter-related bloodstream infections, etc. To author's best knowledge, no validated and standardized methodology evaluating candidate compound activity against staphylococcal biofilms exists. However, a variety of protocols for in vitro drug activity testing has been suggested, yet there are often fundamental differences. Based on our experience, a key methodological step that leads to credible results is to form a robust biofilm with appropriate attributes such as firm adherence to the substrate, a complex arrangement in layers, and the presence of extracellular polysaccharide matrix. At first, for the purpose of drug antibiofilm activity evaluation, the focus was put on various conditions (supplementation of cultivation media by human plasma/fetal bovine serum, shaking mode, the density of initial inoculum) that should lead to reproducible and robust in vitro staphylococcal biofilm formation in microtiter plate model. Three model staphylococcal reference strains were included in the study: Staphylococcus aureus (ATCC 29213), methicillin-resistant Staphylococcus aureus (ATCC 43300), and Staphylococcus epidermidis (ATCC 35983). The total biofilm biomass was quantified using the Christensen method with crystal violet, and results obtained from at least three independent experiments were statistically processed. Attention was also paid to the viability of the biofilm-forming staphylococcal cells and the presence of extracellular polysaccharide matrix. The conditions that led to robust biofilm biomass formation with attributes for biofilms mentioned above were then applied by introducing an alternative method analogous to the commercially available test system, the Calgary Biofilm Device. In this test system, biofilms are formed on pegs that are incorporated into the lid of the microtiter plate. This system provides several advantages (in situ detection and quantification of biofilm microbial cells that have retained their viability after drug exposure). Based on our preliminary studies, it was found that the attention to the peg surface and substrate on which the bacterial biofilms are formed should also be paid to. Therefore, further steps leading to the optimization were introduced. The surface of pegs was coated by human plasma, fetal bovine serum, and L-polylysine. Subsequently, the willingness of bacteria to adhere and form biofilm was monitored. In conclusion, suitable conditions were revealed, leading to the formation of reproducible, robust staphylococcal biofilms in vitro for the microtiter model and the system analogous to the Calgary biofilm device, as well. The robustness and typical slime texture could be detected visually. Likewise, an analysis by confocal laser scanning microscopy revealed a complex three-dimensional arrangement of biofilm forming organisms surrounded by an extracellular polysaccharide matrix.

Keywords: anti-biofilm drug activity screening, in vitro biofilm formation, microtiter plate model, the Calgary biofilm device, staphylococcal infections, substrate modification, surface coating

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Authors: Sina Mahdavi

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Background and Objective: Multiple sclerosis (MS) is the most common inflammatory autoimmune disease of the central nervous system (CNS) that affects the myelination process in the CNS. Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially the John Cunningham virus (JCV) and MS is one potential cause that is not well understood. This study aims to summarize the available data on JCV infection in MS disease progression. Materials and Methods: For this study, the keywords "Multiple sclerosis", " John Cunningham virus ", and "central nervous system" in the databases PubMed, Google Scholar, Sid, and MagIran between 2019 and 2022 were searched, and 12 articles were chosen, studied, and analyzed. Results: MS patients are candidates for natalizumab therapy, which inhibits lymphocyte migration and increases the risk of progressive multifocal leukoencephalopathy (PML), a rare lytic infection of glial cells caused by JCV. Oligodendrocytes may be the target of JCV infection in the central nervous system (CNS). Conclusion: There is a high expression of JCV during the natalizumab treatment period for MS patients, suggesting that the virus may play a role in the development of MS by inducing an inflammatory state. Therefore, it is necessary to evaluate anti-JCV antibody serum as an important risk factor for the development of PML before deciding on the treatment course for these patients.

Keywords: multiple sclerosis, John Cunningham virus, central nervous system, autoimmunity

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Authors: Gouda K. Helal, Marwa I. Shabayek, Heba A. El-Ramly, Heba A. Awida

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The adverse effects of Clindamycin (Clind.) / Ibuprofen (Ibu.) combination on liver, kidney, blood elements and the significances of antioxidants (N-acetylcysteine and Zinc) against these effects were evaluated. The study includes: Group I; control n=30, Group II; patients on Clind.300mg/Ibu.400mg twice daily for a week n=30, Group III; patients on Clind.300mg/Ibu.400mg+N-acetylcysteine 200mg twice daily for a week n=15 and Group IV; patients on Clind.300mg/Ibu.400mg+Zinc50mg twice daily for a week n=15. Serum malondialdehyde (MDA), alanine transferase (ALT), aspartate transferase (AST), γ glutamyl transferase (GGT), creatinine, blood urea nitrogen (BUN) were measured. Applying one way ANOVA followed by Tuckey Kramer post test, Group II showed significant increase in ALT, AST, GGT, BUN and decrease in Hb, RBCs, platelets than Group I. Group III showed significant decrease in ALT, AST, GGT, BUN than Group II. Moreover, Group IV showed significant decrease in ALT, AST, GGT and increase in Hb, RBCs, and platelets than Group II. Conclusively, Adding Zinc or N-acetylcysteine buffer the oxidative stress and improve the therapeutic outcome of Clindamycin/Ibuprofen combination.

Keywords: clindamycin, ibuprofen, adverse effects, antioxidant, zinc, N-acetylcysteine

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Authors: Salim Cerig, Fatime Geyikoglu, Murat Bakir, Suat Colak, Merve Sonmez, Kubra Koc

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Cisplatin (CIS) is one of the most effective an anticancer drug and also toxic to cells by activating oxidative stress. Oleuropein (OLE) has key role against oxidative stress in mammalian cells, but the role of this antioxidant in the toxicity of CIS remains unknown. The aim of the present study was to investigate the efficacy of OLE on CIS-induced liver damages in male rats. With this aim, male Sprague Dawley rats were randomly assigned to one of eight groups: Control group; the group treated with 7 mg/kg/day CIS; the groups treated with 50, 100 and 200 mg/kg/day OLE (i.p.); and the groups treated with OLE for three days starting at 24 h following CIS injection. After 4 days of injections, serum was provided to assess the blood AST, ALT and LDH values. The liver tissues were removed for histological, biochemical (TAC, TOS and MDA) and genotoxic evaluations. In the CIS treated group, the whole liver tissue showed significant histological changes. Also, CIS significantly increased both the incidence of oxidative stress and the induction of 8-hydroxy-deoxyguanosine (8-OH-dG). Moreover, the rats taking CIS have abnormal results on liver function tests. However, these parameters reached to the normal range after administration of OLE for 3 days. Finally, OLE demonstrated an acceptable high potential and was effective in attenuating CIS-induced liver injury. In this trial, the 200 mg/kg dose of OLE firstly appeared to induce the most optimal protective response.

Keywords: antioxidant response, cisplatin, histology, liver, oleuropein, 8-OhdG

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Authors: Hamidreza Khodaei, Ali Daryabeigi Zand

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Conjugated linoleic acid (CLA) is a mixture of isomers of linoleic acid. Despite the fact that 28 different isomers of CLA have already been identified, but the main isomer found in natural diets more than ninety percent CLA on intake of food constitutes demonstrates. CLA is known to be a substance that readily available by rumen microorganisms in some ruminants such as cattle and sheep would likely be made. The main objective of this research was to evaluate the impacts of CLA on lipid metabolism and enhanced fat around the muscle durability by reducing the process of oxidation. In order to implement this research, 80 female mice of the Balb/C, with 55 days of age were employed in the experiment. Treatments include various levels of CLA. Over the course of this study blood samples was also taken from the tail vein of the studied mice. Some other relevant parameters such as serum concentrations of triglycerides, total cholesterol, LDL, HDL and liver enzymes were also determined. The oxidative stability of fats TBARS technique was investigated at different intervals. The findings of the research were analyzed by statistical software of SAS 98. The results, CLA had no significant effect on liver enzymes (P > 0.05). However, it showed a statistically significant impact on triglycerides and total cholesterol. Ratio of LDL to HDL declined remarkably. Histological studies demonstrated reduced accumulation of fat in the tissues surrounding muscles.

Keywords: conjugated linoleic acid, fat metabolism, fat retention, oxidation process

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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: Wei Xiao, Gangzhi Cai, Xingliang Qin, Hongyan Ren, Zaidong Hua, Zhe Zhu, Hongwei Xiao, Ximin Zheng, Jie Yao, Yanzhen Bi

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Myostatin (MSTN) is the master regulator of double muscling phenotype with overgrown muscle and decreased fatness in animals, but its action mode to regulate fat deposition remains to be elucidated. In this study a swin-specific pathway through which MSTN acts to regulate the fat deposition was deciphered. Deep sequenincing of the mRNA and miRNA of fat tissues of MSTN knockout (KO) and wildtype (WT) pigs discovered the positive correlation of myocyte enhancer factor 2C (MEF2C) and fat-inhibiting miR222 expression, and the inverse correlation of miR222 and stearoyl-CoA desaturase 5 (SCD5) expression. SCD5 is rodent-absent and expressed only in pig, sheep and cattle. Fatty acid spectrum of fat tissues revealed a lower percentage of oleoyl-CoA (18:1) and palmitoleyl CoA (16:1) in MSTN KO pigs, which are the catalyzing products of SCD5-mediated desaturation of steroyl CoA (18:0) and palmitoyl CoA (16:0). Blood metrics demonstrated a 45% decline of triglyceride (TG) content in MSTN KO pigs. In light of these observations we hypothesized that MSTN might act through MEF2C/miR222/SCD5 pathway to regulate desaturation of fatty acid as well as triglyceride synthesis in pigs. To this end, real-time PCR and Western blotting were carried out to detect the expression of the three genes stated above. These experiments showed that MEF2C expression was up-regulated by nearly 2-fold, miR222 up-regulated by nearly 3-fold and SCD5 down-regulated by nearly 50% in MSTN KO pigs. These data were consistent with the expression change in deep sequencing analysis. Dual luciferase reporter was then used to confirm the regulation of MEF2C upon the promoter of miR222. Ecotopic expression of MEF2C in preadipocyte cells enhanced miR222 expression by 3.48-fold. CHIP-PCR identified a putative binding site of MEF2C on -2077 to -2066 region of miR222 promoter. Electrophoretic mobility shift assay (EMSA) demonstrated the interaction of MEF2C and miR222 promoter in vitro. These data indicated that MEF2C transcriptionally regulates the expression of miR222. Next, the regulation of miR222 on SCD5 mRNA as well as its physiological consequences were examined. Dual luciferase reporter testing revealed the translational inhibition of miR222 upon the 3´ UTR (untranslated region) of SCD5 in preadipocyte cells. Transfection of miR222 mimics and inhibitors resulted in the down-regulation and up-regulation of SCD5 in preadipocyte cells respectively, consistent with the results from reporter testing. RNA interference of SCD5 in preadipocyte cells caused 26.2% reduction of TG, in agreement with the results of TG content in MSTN KO pigs. In summary, the results above supported the existence of a molecular pathway that MSTN signals through MEF2C/miR222/SCD5 to regulate the fat deposition in pigs. This swine-specific pathway offers potential molecular markers for the development and breeding of a new pig line with optimised fatty acid composition. This would benefit human health by decreasing the takeup of saturated fatty acid.

Keywords: fat deposition, MEF2C, miR222, myostatin, SCD5, pig

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Authors: Mona Marzouk, Nesrine Hegazi, Aliaa Ragheb, Mona El Shabrawy, Salwa Kawashty

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The whole plant of Matthiola longipetala (Brassicaceae) was extracted by 70% methanol to give the total aqueous methanol extract (AME), which was defatted by hexane yielded hexane extract (HE) and defatted AME (DAME). HE was analyzed through GC/MS assay and revealed the detection of 28 non-polar compounds. In addition, the chemical investigation of DAME led to the isolation and purification of twelve flavonoids and three chlorogenic acids. Their structures were interpreted through chemical (complete and partial acid hydrolysis) and spectroscopic analysis (MS, UV, 1D and 2D NMR). Among them, nine compounds have been isolated for the first time from M. longipetala. Moreover, LC-ESI-MS analysis of DAME was achieved to detect additional 46 metabolites, including phospholipids, organic acids, phenolic acids and flavonoids. The biological activity of AME, HE and DAME against alloxan inducing oxidative stress and diabetes in male rats was investigated. Diabetes was induced using a single dose of Alloxan (150 mg/kg b.wt.). HE and DAME significantly increased serum GSH content in rats (37.3±0.7 and 35.9±0.6 mmol/l) compared to diabetic rats (21.8±0.3) and vitamin E (36.2±1.1) at P<0.01. Also, HE, DAME and AME revealed a significant acute anti-hyperglycemic effect potentiated after four weeks of treatment with blood glucose levels of 96.2±5.4, 98.7±6.1 and 98.9±8.6 mg/dl, respectively, compared to diabetic rats (263.4±7.8) and metaformin group (81.9±2.4) at P<0.01.

Keywords: Brassicaceae, Flavonoid, LCMS/MS, Matthiola

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Authors: Richa Jaiswal, Vidisha Sharma, Amulya Rattan, Sushma Sagar, Subodh Kumar, Amit Gupta, Biplab Mishra, Maneesh Singhal

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Background: Adequate nutritional support and daily patient monitoring have an independent therapeutic role in the successful management of high output fistulae and early recovery after abdominal trauma. Case presentation: An 18-year-old girl was brought to AIIMS emergency with alleged history of fall of a heavy weight (electric motor) over abdomen. She was evaluated as per Advanced Trauma Life Support(ATLS) protocols and diagnosed to have significant abdominal trauma. After stabilization, she was referred to Trauma center. Abdomen was guarded and focused assessment with sonography for trauma(FAST) was found positive. Complete duodenojejunal(DJ) junction transection was found at laparotomy, and end-to-end repair was done. However, patient was re-explored in view of biliary peritonitis on post-operative day3, and anastomotic leak was found with sloughing of duodenal end. Resection of non-viable segments was done followed by side-to-side anastomosis. Unfortunately, the anastomosis leaked again, this time due to a post-anastomotic kink, diagnosed on dye study. Due to hostile abdomen, the patient was planned for supportive care, with plan of build-up and delayed definitive surgery. Percutaneous transheptic biliary drainage (PTBD) and STSG were required in the course as well. Nutrition: In intensive care unit (ICU), major goals of nutritional therapy were to improve wound healing, optimize nutrition, minimize enteral feed associated complications, reduce biliary fistula output, and prepare the patient for definitive surgeries. Feeding jejunostomy (FJ) was started from day 4 at the rate of 30ml/h along with total parenteral nutrition (TPN) and intra-venous (IV) micronutrients support. Due to high bile output, bile refeed started from day 13.After 23 days of ICU stay, patient was transferred to general ward with body mass index (BMI)<11kg/m2 and serum albumin –1.5gm%. Patient was received in the ward in catabolic phase with high risk of refeeding syndrome. Patient was kept on FJ bolus feed at the rate of 30–50 ml/h. After 3–4 days, while maintaining patient diet book log it was observed that patient use to refuse feed at night and started becoming less responsive with every passing day. After few minutes of conversation with the patient for a couple of days, she complained about enteral feed discharge in urine, mild pain and sign of dumping syndrome. Dye study was done, which ruled out any enterovesical fistula and conservative management were planned. At this time, decision was taken for continuous slow rate feeding through commercial feeding pump at the rate of 2–3ml/min. Drastic improvement was observed from the second day in gastro-intestinal symptoms and general condition of the patient. Nutritional composition of feed, TPN and diet ranged between 800 and 2100 kcal and 50–95 g protein. After STSG, TPN was stopped. Periodic diet counselling was given to improve oral intake. At the time of discharge, serum albumin level was 2.1g%, weight – 38.6, BMI – 15.19 kg/m2. Patient got discharge on an oral diet. Conclusion: Successful management of post-traumatic proximal high output fistulae is a challenging task, due to impaired nutrient absorption and enteral feed associated complications. Strategic- and goal-based nutrition support can salvage such critically ill patients, as demonstrated in the present case.

Keywords: nutritional monitoring, nutritional support, duodenal fistula, abdominal trauma

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Authors: Vikas Sharma, V. K. Dixit

Abstract:

Anacyclus pyrethrum (A. pyrethrum) has been used as Vajikaran Rasayana (aphrodisiac) in traditional Indian ayurvedic medicine to treat male sexual dysfunction, including infertility. Aphrodisiac activity may be due to an increase in the production or effect of androgens, so this study sought to evaluate the androgenic and spermatogenic potential of the alkylamide-rich ethanol solution extract. Male Wistar strain rats weighing between 150 and 180 g were completely randomized divided into five groups. The ethanol solution extract of A. pyrethrum was administered to groups of rats in 50, 100, and 150 mg/kg doses for a period of 28 days, and the action was compared with control and testosterone-treated rats. Thirteen N-alkylamides were detected in the extract by using HPLC/UV/electrospray ionization mass spectrometry method. Extract administration at all the doses produced significant increase in body weight, sperm count, motility, and viability along with serum testosterone, luteinizing hormone, and follicle-stimulating hormone concentrations. Histoarchitecture of testis revealed increased spermatogenic activities. Seminal fructose content was also significantly increased after 28 days of treatment. Our results suggest that the ethanol solution extract of the roots of A. pyrethrum has androgenic potential and may improve male fertility by enhancing spermatogenesis.

Keywords: N-alkylamides, testosterone, Anacyclus pyrethrum, androgen

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Authors: Jihene Bettaieb, Kaouther Ayouni, Ghassen Kharroubi, Rym Mallekh, Walid Hammemi, Afif Ben Salah, Henda Triki

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In Tunisia, the hepatitis A virus (HAV) represents a public health concern. Due to the progress in sanitation and socio-economic conditions, the epidemiology of HAV has shown dynamic changes over the past years. This study aimed to investigate the current seroprevalence of HAV antibodies (anti-HAV) among the residents of Thala, a rural setting in central-west Tunisia, to determine the age-specific seroprevalence for HAV infection and co-infection with hepatitis C and B virus. A total of 1379 subjects (mean age: 25.0 ± 17.3 years, 555 males/ 824 females) were recruited between January and June 2014. The study population included 95 individuals previously known as hepatitis C positive. Serum samples were collected and screened for the detection of IgG anti-HAV, HBsAg, and HBcAb by the Elisa Test. The overall anti- HAV seroprevalence was about 84.7%. There was no statistically significant difference between males and females. On the 1379 tested individual, 219 were positive for HBcAb, and 67 were positive for HBsAg. IgG anti- HAV were positive in 80.6% of HBsAg-positive patients (54 out of 67), 81.3% of HBcAb-positive patients (178 out of 219), and in 95.8% of HCV-positive patients (91 out of 95). HBV infection and HCV infection were statistically associated with a greater risk of positive anti-HAV antibody (p < 0.001). Our study revealed that Thala represents an intermediate endemicity level and that the introduction of vaccination against HAV in this region is recommended, especially for the hepatitis B or C infected person seronegative for HAV.

Keywords: coinfection, hepatitis A, seroprevalence, Tunisia

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Authors: Ali Babaei Zarch, S. Kianbakht, H. Fallah Huseini, P. Changaei, A. Mirjalili, J. Salehi

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Background: Malva sylvestris L. is widely used in the traditional medicine of Iran and other countries to treat gastrointestinal, respiratory, skin and urological Disorders. Moreover, it has antioxidant property. Objective: In this study the protective effect of Malva sylvestris against sodium fluoride-induced nephrotoxicity in rats were evaluated. Methods: The Malva sylvestris flower extract was injected intraperitoneally at the doses of 100, 200, 400 mg/kg/day to groups of rats ( 10 in each group) for 1 week and subsequently 600 ppm sodium fluoride was added daily to the rats drinking water for 1 additional week. After these steps, the rats’ serum levels of urea, creatinine, reduced glutathione, catalase and malondialdehyde were determined. The histopathology of the rats’ kidney was also studied. Results: Malva sylvesteries extract with doses of 400 mg/kg/day significantly decreased the urea and creatinine levels (P<0.05). Moreover, the levels of catalase and glutathione were increased by this dose, but only the catalase increase was statistically significant (P<0.05). All three extract doses of Malva decreased the malondialdehyde level, but it was significant only for the dose 400 mg/kg/day (P<0.05). Histopathological findings also showed a protective effect of Malva against renal damage induced by sodium fluoride. Conclusion: The results suggest that Malva sylvestris has a protective effect against sodium fluoride-induced nephrotoxicity through its antioxidant property.

Keywords: Malva sylvestris, mephrotoxicity, sodium fluoride, rat  

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Authors: Muhammad Imran Hussain, Ramisha Ibtisam, Tayyaba Fatima, Huba Khalid, Ayesha Aziz, Khansa, Adan Sitara, Anam Shahzad, Aymen Jabeen

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Vitamin D supports the immune system fight TB by inhibiting Interferon-gamma (IFN-γ) and lowering host inflammation. The purpose of the research was to see if giving the vitamin D supplements to TB patients affected their prognosis. A randomized placebo control study of 200 TB patients was performed among which 106 received 400,000 IU of injectable vitamin D3 and 94 received placebo for 2 doses. Assessment was carried out at the end of every month for 3 months. IFN-γ responses to whole blood stimulation generated by the Mycobacterium tuberculosis sonicate (MTBs) antigen and early secreted and T cell activated 6 kDa (ESAT6) were assessed at 0 and 12 weeks. The statistical analysis used descriptive statistics (mean and standard deviation), Friedman's test and Fisher's test. The vitamin D group gained significantly more weight (+3.90 pounds) and had less persistent lung disease on imaging (1.33 zones vs. 1.84 zones). They also had a 50% decrease in cavity size. Additionally, patients with low baseline serum concentrations of 25-(OH)D had a significant increase in MTB-induced IFN-γ production after taking vitamin D supplements. Vitamin D administration in large amounts can hasten the recovery of TB patients. The findings point is a therapeutically useful activity of Vitamin D's in the management for tuberculosis.

Keywords: tuberculosis, vitamin D, interferon gamma, protein, infection

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Authors: Lynn Lehmann, Dinorah Leyva, Ana Lazic, Stefan Duhr, Philipp Baaske

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Characterization of biomolecular interactions, such as protein-protein, protein-nucleic acid or protein-small molecule, provides critical insights into cellular processes and is essential for the development of drug diagnostics and therapeutics. Here we present a novel, label-free, and tether-free technology to analyze picomolar to millimolar affinities of biomolecular interactions by Microscale Thermophoresis (MST). The entropy of the hydration shell surrounding molecules determines thermophoretic movement. MST exploits this principle by measuring interactions using optically generated temperature gradients. MST detects changes in the size, charge and hydration shell of molecules and measures biomolecule interactions under close-to-native conditions: immobilization-free and in bioliquids of choice, including cell lysates and blood serum. Thus, MST measures interactions under close-to-native conditions, and without laborious sample purification. We demonstrate how MST determines the picomolar affinities of antibody::antigen interactions, and protein::protein interactions measured from directly from cell lysates. MST assays are highly adaptable to fit to the diverse requirements of different and complex biomolecules. NanoTemper´s unique technology is ideal for studies requiring flexibility and sensitivity at the experimental scale, making MST suitable for basic research investigations and pharmaceutical applications.

Keywords: biochemistry, biophysics, molecular interactions, quantitative techniques

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Authors: Barbosa M. L. S., von Ancken A. C. B., Coelho C. P.

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In order to improve the treatment of epileptic dogs, this case report aims toobjective todescribe the use of the homeopathic medicine Cicuta virosa for the treatmentof seizuresin dogs that already use allopathy to control them. Howeach patient presents symptoms individually, the choice of medicationhomeopathic treatment must also be individualized. He was treated in the municipality of RibeirãoPires, São Paulo - Brazil, an animal of the canine species, female, 7 years old, SRD, with a history of seizuregeneralized tonic-clonic for two years, with a variable frequency of 1-2 seizures perday. With no identifiable etiology, the patient used phenobarbital daily, and the dose ofmedication was increased according to the frequency of seizures. The serum concentration of phenobarbital within 12 hours of itsadministration via blood sample was within the range ofreference. The patient experienced weight gain and intermittent sedation. the choice ofhomeopathic medicine Cicuta virosa 6 cH, prepared according to the PharmacopoeiaBrazilian Homeopathic Medicine, occurred due to its characteristic action on the nervous system, especially in epileptic animals that present with seizures, spasmodic contractions of the muscles of the whole body starting from the head, mouth, extremely violent, with rigidity and opisthotonos, extreme agitation, contortionsmultiple. The animal was submitted to treatment with 2 globules orally twicea day for 30 days. The treatment resulted in a clinical cure as there was no moreseizures, being effective to control this symptom.

Keywords: homeopathy, cicuta virosa, epilepsy, veterinary medicine

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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: Li Bixia, Ren Shouwen, Fu Yanfeng, Tu Feng, Xiaoming Fang, Xueming Wang

Abstract:

The utilization of dietary crude fiber in different breed pigs is not the same. Su-shan pigs are a new breed formed by crossing Taihu pigs and Yorkshire pigs. In order to understand the resistance of Su-shan pigs to dietary crude fiber, 150 Su-shan pigs with 60 kg of average body weight and similar body conditions were allocated to three groups randomly, and there are 50 pigs in each group. The percentages of dietary crude fiber were 8.35%, 9.10%, and 11.39%, respectively. At the end of the experiment, 15 pigs randomly selected from each group were slaughtered. The results showed as follows: average daily gain of the 9.10% group was higher than that of the 8.35% group and the 11.39% group; there was a significant difference between the 9.10% group and the 8.35% group (p < 0.05. Levels of urea nitrogen, total cholesterol and high density lipoprotein in the 9.10% group were significantly higher than those in the 8.35% group and the 11.39% group (p < 0.05). Ratios of meat to fat in the 9.10% group and the 11.39% group were significantly higher than that in the 8.35% group (p < 0.05). Lean percentage of 9.10% group was higher than that of 8.35% group and 11.39% group, but there was no significant difference in three groups (p > 0.05). The weight of small intestine and large intestine in the 11.39% group was higher than that in the 8.35% group, and the 9.10% group and the difference reached a significant level (p < 0.05). In conclusion, increasing dietary crude fiber properly could reduce fat percentage, and improve the ratio of meat to fat of finishing Su-shan pigs. The digestion and metabolism of dietary crude fiber promoted the development of stomach and intestine of finishing Su-shan pig.

Keywords: Su-shan pigs, dietary crude fiber, growth performance, serum biochemical indexes

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Authors: Kolja Them, Priyal Chikhaliwala, Sudeshna Chandra

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Purpose: The purpose of this work is to examine possibilities for noninvasive imaging and identification of tumor markers for cancer diagnosis. The proposed method uses antibody conjugated iron oxide nanoparticles and multicolor Magnetic Particle Imaging (mMPI). The method has the potential for radiation exposure free real-time estimation of local tumor marker concentrations in vivo. In this study, the method is applied to human Alpha-1-Fetoprotein. Materials and Methods: As tracer material AFP antibody-conjugated Dendrimer-Fe3O4 nanoparticles were used. The nanoparticle bioconjugates were then incubated with bovine serum albumin (BSA) to block any possible nonspecific binding sites. Parts of the resulting solution were then incubated with AFP antigen. MPI measurements were done using the preclinical MPI scanner (Bruker Biospin MRI GmbH) and the multicolor method was used for image reconstruction. Results: In multicolor MPI images the nanoparticles incubated only with BSA were clearly distinguished from nanoparticles incubated with BSA and AFP antigens. Conclusion: Tomographic imaging of human tumor marker Alpha-1-Fetoprotein is possible using AFP antibody conjugated iron oxide nanoparticles in presence of BSA. This opens interesting perspectives for cancer diagnosis.

Keywords: noninvasive imaging, tumor antigens, antibody conjugated iron oxide nanoparticles, multicolor magnetic particle imaging, cancer diagnosis

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Authors: M. Golzade Gangraj, A. Abdi, N. ganji

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Aim: The aim of this study was to evaluate the Effect of aerobic training with Coriandrum sativum extract on selection of oxidative stress markers in diabetic rats. Methods: The population of male Wistar rats is the Pasteur Institute. Forty rats were randomly selected as subjects. After moving the mouse in vitro and stay for a week in a cage for sustainability, were diabetic. Diabetes induced by injection STZ (55 mg per kg of body weight of mice) was performed. According blood glucose was randomly divided into four experimental groups (control, training, extract and training-extract). Extract group consumed 150 mg per kg of body weight per day coriander juice. Training group performed aerobic training (50-55% VO2max). Result: The results showed that aerobic exercise training and coriander seed extract caused a significant increase in total antioxidant; superoxide dismutase and catalase were significantly decreased malondialdehyde. Conclusion: the research findings can be stated that the exercise with coriander seed extract has the ability to inhibit free radicals and can have beneficial effects on the body's antioxidant defense system and reduce oxidative stress in diabetic rats with STZ. Because it improves the body's antioxidant defense by increasing serum levels of antioxidant enzymes.

Keywords: aerobic training, coriandrum sativum, antioxidant, diabetes

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