Search results for: inflammatory myopathies

Authors: A. Ratika Thakur, B. A. K. Sinha , C. R. K. Pathak

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Reproductive Tract Infections are recognized as a serious global health problem with direct impact on women. In the developing countries, prevalence of RTI is much higher relative to other health problems. Women of the reproductive age group are socially, mentally and physically more vulnerable to infections. Also, it is a well established fact that RTI has prolonged complications in women rather than men. It causes ectopic pregnancy, pelvic inflammatory diseases, miscarriage and infertility in the long course. Women perspective about infections is less studied. In this view the study was carried out with an aim to determine knowledge, perception and belief of married women towards reproductive tract infection. The study was conducted in Junga village, District Shimla, Himachal Pradesh, India. 48 women were interviewed regarding awareness, beliefs and taboos related to reproductive tract infection. Other aspects like fertility history were also taken into account. The data were collected using interviews with the help of interview schedule and interview guide. Data were recorded in the form of narratives and case studies. The analysis was done using quantitative and qualitative analysis. It was found that a majority of women were not aware about the reasons of infection. Moreover cultural beliefs, perceptions and taboos made them more vulnerable and exposed to RTI. Economic dependency upon men, lack of control in barrier methods were some of the factors that contributed to delayed treatment of women. It was found that a majority of women suffering from RTIs were silently bearing the burden and underwent treatment when the case would not rest in their hands.

Keywords: belief, infection, perception, taboo, women

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Authors: Marzieh Fotovvat, Farzaneh Najafi, Ramazan Ali Khavari-Nejad, Daryush Talei, Farhad Rejali

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Salvia leriifolia Benth. is one of the valuable and perennial medicinal plants of the Lamiaceae family, geographically growing in the south and tropical regions of Khorassan and Semnan provinces in Iran. In recent years, several medicinal properties such as antimicrobial, antifungal, anti-diabetic, analgesic, and anti-inflammatory effects have been reported from this plant. The use of elicitors such as chitosan and Arbuscular mycorrhizal fungi (AMF) symbiosis are the main methods for increasing the production of secondary metabolites, growth, and physiological factors in plants. The main aim of this study was to investigate the effects of foliar spraying applications by chitosan and/or the contribution of AMF (Glomus interaradices) on some growth factors and chlorophyll content of S. leriifolia under glasshouse conditions. The sterilized seeds were germinated by placing them into a cocopeat. After one month, seedlings that were in the 2-4 leaf stage were transferred to plastic pots (garden soil and pumice at 2:1) with or without mycorrhizal fungi. Chitosan (0, 50, 100, 200, and 400 mg L-1) was sprayed four times in the fourth month of the vegetative period. The results showed that fresh leaf weight, fresh root weight, root height, and chlorophyll content could change in the plant treated with chitosan and AMF symbiosis. So that the highest chlorophyll content and fresh weight of roots and leaves were observed in the interaction of chitosan and G. interaradices. In general, by optimizing the chitosan concentration and the use of appropriate AMF symbiosis, it is possible to improve the growth and quality of the medicinal plant S. leriifolia.

Keywords: chitosan, chlorophyll, growth factors, mycorrhiza

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Authors: H. Aldewachi, M. Hines, M. McCulloch, N. Woodroofe, P. Gardiner

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DPP-IV is an enzyme whose expression is affected in a variety of diseases, therefore, has been identified as possible diagnostic or prognostic marker for various tumours, immunological, inflammatory, neuroendocrine, and viral diseases. Recently, DPP-IV enzyme has been identified as a novel target for type II diabetes treatment where the enzyme is involved. There is, therefore, a need to develop sensitive and specific methods that can be easily deployed for the screening of the enzyme either as a tool for drug screening or disease marker in biological samples. A variety of assays have been introduced for the determination of DPP-IV enzyme activity using chromogenic and fluorogenic substrates, nevertheless these assays either lack the required sensitivity especially in inhibited enzyme samples or displays low water solubility implying difficulty for use in vivo samples in addition to labour and time-consuming sample preparation. In this study, novel strategies based on exploiting the high extinction coefficient of gold nanoparticles (GNPs) are investigated in order to develop fast, specific and reliable enzymatic assay by investigating synthetic peptide sequences containing a DPP IV cleavage site and coupling them to GNPs. The DPP IV could be detected by colorimetric response of peptide capped GNPs (P-GNPS) that could be monitored by a UV-visible spectrophotometer or even naked eyes, and the detection limit could reach 0.01 unit/ml. The P-GNPs, when subjected to DPP IV, showed excellent selectivity compared to other proteins (thrombin and human serum albumin) , which led to prominent colour change. This provided a simple and effective colorimetric sensor for on-site and real-time detection of DPP IV.

Keywords: gold nanoparticles, synthetic peptides, colorimetric detection, DPP-IV enzyme

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Authors: Mohammad Jamal

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Non-alcoholic fatty liver disease (NAFLD) has become one of the most chronic liver diseases, prevalent among people with morbid obesity. NAFLD does not develop clinically significant liver disease, however cirrhosis and liver cancer develop in subset and currently there are no approved therapies for the treatment of NAFLD. The study is aimed to understand the various key genes involved in the mechanism of NAFLD which can be valuable for developing diagnostic and predictive biomarkers based on their histologic stage of liver. The study was conducted on 16 male Sprague Dawley rats. The animals were divided in two groups: control group (n=8) fed on ad libitum normal chow and regular water and the cafeteria group (CAF)) (n=8) fed on high fatty/ carbohydrate diet. The animals received their respective diet from 4 weeks onwards from D.O.B until 25 weeks. Liver was extracted and RT² Profiler PCR Array was used to assess the NAFLD related genes. Histological evaluation was performed using H&E stain in liver tissue sections. Our PCR array results showed that genes involved in anti-inflammatory activity (Ifng, IL10), fatty acid uptake/oxidation (Fabp5), apoptosis (Fas), lipogenesis (Gck and Srebf1), Insulin signalling (Igfbp1) and metabolic pathway (pdk4) were upregulated in the liver of cafeteria fed obese rats. Bloated hepatocytes, displaced nucleus and higher lipid content were seen in the liver of cafeteria fed obese rats. Although Liver biopsies remain the gold standard in evaluating NAFLD, however an approach towards non-invasive markers could be used in understanding the physiology, therapeutic potential, and the targets to combat NAFLD.

Keywords: biomarkers, cafeteria diet, obesity, NAFLD

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Authors: Qiaofeng Guo

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Aims: Obesity is often accompanied by insulin resistance (IR) and whole-body inflammation. Aerobic exercise is an effective treatment to improve insulin resistance and inflammation. However, the anti-inflammatory mechanisms of exercise on epididymal and subcutaneous adipose remain to be elucidated. Here, we compared the macrophage polarization between epididymal and subcutaneous adipose after aerobic exercise. Methods: Male C57BL/6 mice were fed a normal diet group or a high-fat diet group for 12 weeks and performed aerobic training on a treadmill at 55%~65% VO₂ max for eight weeks. Food intake, body weight, and fasting blood glucose levels were monitored weekly. The intraperitoneal glucose tolerance test was to evaluate the insulin resistance model. Fat mass, blood lipid profile, serum IL-1β, TNF-α levels, and CD31/CD206 rates were analysed after the intervention. Results: FBG (P<0.01), AUCIPGTT (P<0.01), and HOMA-IR (P<0.01) increased significantly for a high-fat diet and decreased significantly after the exercise. Eight weeks of aerobic exercise attenuated HFD-induced weight gain and glucose intolerance and improved insulin sensitivity. Serum IL-1β, TNF-α, CD11C/CD206 expression in subcutaneous adipose tissue were not changed before and after exercise, but not in epididymal adipose tissue (P<0.01). Conclusion: Insulin resistance is not accompanied by chronic inflammation and M1 polarization of subcutaneous adipose tissue macrophages in high-fat diet mice. Aerobic exercise effectively improved lipid metabolism and insulin sensitivity, which may be closely associated with reduced M1 polarization of epididymal adipose macrophages.

Keywords: aerobic exercise, insulin resistance, chronic inflammation, adipose, macrophage polarization

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Authors: Alaa E. El-sisi, Sherin Zakaria

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Rebamipide is an antiulcer drug with unique properties such as anti-inflammatory action. It induces endogenous prostaglandin e2 (PGE2). PGE2 is considered as a potent physiological suppressor of liver fibrosis. Aim of study: This study investigated the effect of rebamipide on hepatic fibrosis. Material and Method: Hepatic fibrosis was induced by intraperitoneal injections (IP) injection of CCl4 (0.45 mL/kg) in corn oil 1:5 twice a week for 4 weeks. Rats were divided into four groups as follow: Group 1 treated with CCL4 only, group 2 and 3 treated with CCL4 and rebamipide 60 mg/kg/day (group2) or 100 mg/kg/day (group3), and the fourth group was considered as control group and treated with vehicles. ALT, AST, and Bilirubin were assayed in serum. Antioxidant markers such as malondialdhyde (MDA) and superoxide dismutase (SOD) and fibrotic markers such as hyaluronic acid (HA) and procollagen-III (procol-III) were evaluated in liver tissues. IL-10 as well as PGE2 were also assayed in liver tissues. Pathologic changes in the liver were detected by hematoxylin and eosin staining. Collagen precipitation in liver tissues was visualized using masson trichrom stain. Results: Rebamipide inhibit CCL4 induced increase in ALT and AST significantly (p < 0.05). Rebamipide exerted an antioxidant effect as it inhibits CCL4 induced increased MDA level and decreased SOD activity. Fibrotic markers assay revealed that repamipide (60 or 100 mg/kg/day) decreased the level of procol-III and HA compared to CCl4 (p < 0.05). Oral administration of Rebamipide was associated with a significant increase (p < 0.05) of PGE2 and IL-10. Rebamipide especially at the dose of (100 mg/kg/day) restores liver histology structure and abolish collagen precipitation in liver tissues. Conclusion: Rebamipide retards hepatic fibrosis induced by CCL4 may be through the induction of PGE2 level.

Keywords: fibrotic markers, hepatic fibrosis, PGE2, rebamipide

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Authors: Xiao Wei, Dandan Sheng, Xiaoyan Jiang, Lili Gui, Huizhu Wang, Xi Yu, Hailiang Liu, Min Hong

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Objective: Mice Type2 allergic contact dermatitis was utilized in this study to explore the effect of AS-IV on Type 2 allergic inflammatory. Methods: The mice were topically sensitized on the shaved abdomens with 1.5% FITC solution on abdominal skin in the day 1 and day 2 and elicited on the right ear with 0.5% FITC solution at day 6. Mice were treated with either AS-IV or normal saline from day 1 to day 5 (induction phase). Auricle swelling was measured 24 h after the elicitation. Ear pathohistological examination was carried out by HE staining. IL-4\IL-13, and IL-9 levels of ear tissue were detected by ELISA. Mice were treated with AS-IV at the initial stage of induction phase, ear tissue was taked at day 3.TSLP level of ear tissue was detected by ELISA and TSLPmRNA\NF-kBmRNA\TLRs（TLR2\TLR3\TLR8\TLR9）mRNA were detected by PCR. Results: AS-IV induction phase evidently inhibited the auricle inflam-mation of the models; pathohistological results indicated that AS-IV induction phase alleviated local edema and angiectasis of mice models and reduced lymphocytic infiltration. AS-IV induction phase markedly decreased IL-4\IL-13, and IL-9 levels in ear tissue. Moreover, at the initial stage of induction pha-se, AS-IV significantly reduced TSLP\TSLPmRNA\NF-kBmRNA\TLR2mRNA\TLR8 mRNA levels in ear tissue. Conclusion: Administration with AS-IV in induction phase could inhibit Type 2 allergic contact dermatitis in mice significantly, and the mechanism may be related with regulating TSLP through TLRs-NF-kB pathway.

Keywords: Astragaioside IV, allergic contact dermatitis, TSLP, interleukin-4, interleukin-13, interleukin-9

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Authors: Yang Zhao, Feng Zhang, Xuanchu Duan

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Trans-differentiation of human Tenon fibroblasts (HTFs) to myo-fibroblasts and fibrosis of episcleral tissue are the most common reasons for the failure of glaucoma filtration surgery, with limited treatment options like antimetabolites which always have side-effects such as leakage of filter bulb, infection, hypotony, and endophthalmitis. Rosiglitazone, a specific thiazolidinedione is a synthetic high-affinity ligand for PPAR-r, which has been used in the treatment of type2 diabetes, and found to have pleiotropic functions against inflammatory response, cell proliferation and tissue fibrosis and to benefit to a variety of diseases in animal myocardium models, steatohepatitis models, etc. Here, in vitro we cultured primary HTFs and stimulated with TGF- β to induced myofibrogenic, then treated cells with Rosiglitazone to assess for fibrogenic response. In vivo, we used rabbit glaucoma model to establish the formation of post- trabeculectomy scarring. Then we administered subconjunctival injection with Rosiglitazone beside the filtering bleb, later protein, mRNA and immunofluorescence of fibrogenic markers are checked, and filtering bleb condition was measured. In vitro, we found Rosiglitazone could suppressed proliferation and migration of fibroblasts through macroautophagy via TGF- β /Smad signaling pathway. In vivo, on postoperative day 28, the mean number of fibroblasts in Rosiglitazone injection group was significantly the lowest and had the least collagen content and connective tissue growth factor. Rosiglitazone effectively controlled human and rabbit fibroblasts in vivo and in vitro. Its subconjunctiiva application may represent an effective, new avenue for the prevention of scarring after glaucoma surgery.

Keywords: fibrosis, glaucoma, macroautophagy, rosiglitazone

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Authors: Patompong Satapornpong, Therdpong Tempark, Pawinee Rerknimitr, Jettanong Klaewsongkram, Chonlaphat Sukasem

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Dapsone (4, 4’-diaminodiphenyl sulfone, DDS) is broadly used for the treatment of inflammatory diseases and infections such as; leprosy, Pneumocystis jiroveci pneumonia in patients with HIV infection, neutrophilic dermatoses, dermatitis herpetiformis and autoimmune bullous disease. The severe cutaneous adverse drug reactions (SCARs) including, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) are rare but severe life-threatening adverse drug reactions. Dapsone is one of many culprit drugs induced SJS, TEN and DRESS. Notwithstanding, to our knowledge, there are no studies of the association of HLA class I alleles and dapsone-induced SCARs in non-leprosy Thai patients. This investigation was a prospective cohort study, which performed in a total of 45 non-leprosy patients. Fifteen patients of dapsone-induced SCARs were classified as following the RegiSCAR criteria, and 30 dapsone-tolerant controls were exposed to dapsone more than 6 months without any evidence of cutaneous reactions. The genotyping of HLA-A, -B and –C were performed using sequence-specific oligonucleotides (PCR-SSOs). The Ethics Committee of Ramathibodi hospital, Mahidol University, approved this study. Among all HLA class I alleles, HLA-A*24:07, HLA-B*13:01, HLA-B*15:02, HLA-C*03:04 and HLA-C*03:09 were significantly associated with dapsone-induced SCARs (OR = 10.55, 95% CI = 1.06 – 105.04, p = 0.0360; OR = 56.00, 95% CI = 8.27 – 379.22, p = 0.0001; OR = 7.00, 95% CI = 1.17 – 42.00, p = 0.0322; OR = 6.00, 95% CI = 1.24 – 29.07, p = 0.0425 and OR = 17.08, 95% CI = 0.82 – 355.45, p = 0.0321, respectively). Furthermore, HLA-B*13:01 allele had strong association with dapsone-induced SJS-TEN and DRESS when compared with dapsone-tolerant controls (OR = 42.00, 95% CI = 2.88 – 612.31, p = 0.0064 and OR = 63.00, 95% CI = 7.72 – 513.94 and p = 0.0001, respectively). Consequently, HLA-B*13:01 might serve as a pharmacogenetic marker for screening before initiating the therapy with dapsone for prevention of dapsone-induced SCARs.

Keywords: dapsone-induced SCARs, HLA-B*13:01, HLA class I alleles, severe cutaneous adverse reactions, Thai

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Authors: Suraj Muke, Vikas Mankumare, Sadhana Sathaye

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Osteoporosis is the most common metabolic bone disease which affects an estimated 25 million people worldwide, leading to 1 million fractures, 40,000 annual deaths and health costs of billions of dollars. It is estimated that about 80% of total osteoporosis patients are women, amongst which majority are above the age of 45 years. Postmenopausal osteoporosis is associated with lack of intestinal calcium absorption, increasing pro-oxidant and inflammatory mediators. Lawsonia inermis is a biennial dicotyledonous herbaceous shrub is reported to possess a high flavonoid, high phenolic and Inhibitors of osteoclastogenesis like Daphneside and Daphnorin. The present study aimed to screen osteoprotective effect of methanolic extract of Lawsonia inermis (LIM) in rat model along with its antioxidant activity. LIM shows phenolic content 146.3Milligrams of Gallic acid equivalent present per gram of extract and 19.8 Milligrams of rutin per gram of extract of Total flavonoid content with IC50 value 42.99μg/ml. bilateral ovariectomized rat model in which Healthy female wistar rats were used for screening. Treatment with LIM was carried out using graded doses of 25mg/kg, 50mg/kg and 100mg/kg for period of 28 days. The negative control group comprised of ovariectomized rats along with saline treatment for four weeks whereas sham operated rats were used as positive control.LIM showed a decrease in bone turnover by preventing loss of urinary calcium and phosphorous moreover it decreased the alkaline phosphatase levels and loss of bone density is prevented by LIM suggesting decrease in osteoclast activity.

Keywords: antioxidant, osteoclast, osteoporosis, ovariectomized

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Authors: Nalan Kaya, Elif Erdem, Mehmet Ali Kisacam, Gonca Ozan, Enver Ozan

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Tobacco smokers continuously inhale thousands of carcinogens and free radicals. It is estimated that about 1017 oxidant molecules are present in each puff of tobacco smoke. It is known that smoking has adverse effects on the structure and functions of the liver. Ellagic acid (EA) has antioxidant, antiapoptotic, anticarcinogenic, antibacterial and antiinflammatory effects. The aim of our study was to investigate the possible protective effect of ellagic acid against tobacco smoke-mediated oxidative stress in the rat liver. Twenty-four male adult (8 weeks old) Spraque-Dawley rats were divided randomly into 4 equal groups: group I (control), group II (tobacco smoke), group III (tobacco smoke + corn oil) and group IV (tobacco smoke + ellagic acid). The rats in group II, III and IV, were exposed to tobacco smoke 1 hour twice a day for 12 weeks. In addition to tobacco smoke exposure, 12 mg/kg ellagic acid (dissolved in corn oil), was applied to the rats in group IV by oral gavage. An equal amount of corn oil used in solving ellagic acid was applied to the rats by oral gavage in group III. At the end of the experimental period, rats were decapitated, and liver tissues were removed. Histological and biochemical analyzes were performed. Sinusoidal dilatation, inflammatory cell infiltration in portal area, increased Kuppfer cells were examined in tobacco smoke group and tobacco smoke+ corn oil groups. The results, observed in tobacco smoke and tobacco smoke+corn oil groups, were found significantly decreased in tobacco smoke+EA group. Group-II and group-III MDA levels were significantly higher, and GSH activities were not different than group-I. Compared to group-II, group-IV MDA level was decreased, and GSH activities was increased significantly. The results indicate that ellagic acid could protect the liver tissue from the tobacco smoke harmful effects.

Keywords: ellagic acid, liver, rat, tobacco smoke

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Authors: G. A. Ravishankar, A. Ramakrishna

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Melatonin (MEL) and Serotonin (SER), also known as [5-Hydroxytryptamine (5-HT)] are reported to be in a range of plant types which are edible. Their occurrence in plants species appears to be ubiquitous. Their presence in high quantities in plants assumes significance owing to their physiological effects upon consumption by human beings. MEL is a well known animal hormone mainly released by the pineal gland known to influence circadian rhythm, sleep, apart from immune enhancement. Similarly, SER is a neurotransmitter that regulates mood, sleep and anxiety in mammals. It is implicated in memory, behavioral changes, scavenging reactive oxygen species, antipsychotic, etc. Similarly Role of SER and MEL in plant morphogenesis, and various physiological processes through intense research is beginning to unfold. These molecules are in common foods viz banana, pineapple, plum, nuts, milk, grape wine. N- Feruloyl serotonin and p-coumaroyl serotonin found in certain seeds are found to possess antioxidant, anti-inflammatory, antitumor, antibacterial, and anti-stress potential apart from reducing depression and anxiety. MEL is found in Mediterranean diets, nuts, cherries, tomato berries, and olive products. Consumption of foods rich in MEL is known to increase blood MEL levels which have been implicated in protective effect against cardiovascular damage, cancer initiation and growth. MEL is also found in wines, green tea, beer, olive oil etc. Moreover, presence of SER and MEL in Coffee beans (green and roasted beans) and decoction has been reported us. In this communication we report the occurrence of indole amines in edible plants and their implications in human health.

Keywords: serotonin, melatonin, edible plants, neurotransmitters, physiological effects

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Authors: Addisu Tadesse Sahile, Tennyson Mgutshini

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Background: Periodontal disease is a common, complex, inflammatory disease characterized by the destruction of tooth-supporting soft and hard tissues of the periodontium and a major public health problem across developed and developing countries. Objectives: The study was aimed at assessing the prevalence of periodontal disease and associated factors among diabetes patients in Addis Ababa, Ethiopia, 2018. Methods: Institutional based cross-sectional study was conducted on 388 diabetes patients selected by systematic random sampling method from March to May 2018. The study was conducted at two conveniently selected public hospitals in Addis Ababa. Data were collected with pre-tested, structured and translated questionnaire then entered to SPSS version 23 software for analysis. Descriptive statistics as a summary, in line with chi-square and binary logistics regression to identify factors associated with periodontal disease, were applied. A 95% CI with a p-value less than 5% was used as a level of significance. Results: Ninety-one percent (n=353) of participants had periodontal disease while oral examination was done in six regions. While only 9% (n=35) of participants were free of periodontal disease. The number of tooth brushings per day, correct techniques of brushing, malocclusion, and fillings that are defective were associated with periodontal disease at p < 0.05. Conclusion and recommendation: A higher prevalence of periodontal disease among diabetes patient was observed. The frequency of tooth brushing, correct techniques of brushing, malocclusion and defective fillings were associated with periodontal disease. Emphasis has to be given to oral health of diabetes patients by every concerned body so as to control the current higher burden of periodontal disease in diabetes.

Keywords: periodontal disease, risk factors, diabetes mellitus, Addis Ababa

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Authors: Krishna Pal Singh, Shailendra Kumar Gupta, Olaf Wolkenhauer

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Background: Our study aimed to identify common genes and potential targets across the four diseases, which include rheumatoid arthritis, melanoma metastasis, ulcerative colitis, and Crohn’s disease. We used a network and systems biology approach to identify the hub gene, which can act as a potential target for all four disease conditions. The regulatory network was extracted from the PPI using the MCODE module present in Cytoscape. Our objective was to investigate the significance of hub genes in these diseases using gene ontology and KEGG pathway enrichment analysis. Methods: Our methodology involved collecting disease gene-related information from DisGeNET databases and performing protein-protein interaction (PPI) network and core genes screening. We then conducted gene ontology and KEGG pathway enrichment analysis. Results: We found that IL6 plays a critical role in all disease conditions and in different pathways that can be associated with the development of all four diseases. Conclusions: The theoretical importance of our research is that we employed various systems and structural biology techniques to identify a crucial protein that could serve as a promising target for treating multiple diseases. Our data collection and analysis procedures involved rigorous scrutiny, ensuring high-quality results. Our conclusion is that IL6 plays a significant role in all four diseases, and it can act as a potential target for treating them. Our findings may have important implications for the development of novel therapeutic interventions for these diseases.

Keywords: melanoma metastasis, rheumatoid arthritis, inflammatory bowel diseases, integrated bioinformatics analysis

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Authors: Surbhi Aggarwal, Jaishree Paul

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Background: Role of GABA has been implicated in autoimmune diseases like multiple sclerosis, type1 diabetes and rheumatoid arthritis where they modulate the immune response but role in gut inflammation has not been defined. Ulcerative colitis (UC) and diarrhoeal predominant irritable bowel syndrome (IBS-D) both involve inflammation of gastrointestinal tract. UC is a chronic, relapsing and idiopathic inflammation of gut. IBS is a common functional gastrointestinal disorder characterised by abdominal pain, discomfort and alternating bowel habits. Mild inflammation is known to occur in IBS-D. Aim: Aim of this study was to investigate the role of GABA in UC as well as in IBS-D. Materials and methods: Blood and biopsy samples from UC, IBS-D and controls were collected. ELISA was used for measuring level of GABA in serum of UC, IBS-D and controls. RT-PCR analysis was done to determine GABAergic signal system in colon biopsy of UC, IBS-D and controls. RT-PCR was done to check the expression of proinflammatory cytokines. CurveExpert 1.4, Graphpad prism-6 software were used for data analysis. Statistical analysis was done by unpaired, two-way student`s t-test. All sets of data were represented as mean± SEM. A probability level of p < 0.05 was considered statistically significant. Results and conclusion: Significantly decreased level of GABA and altered GABAergic signal system was detected in UC and IBS-D as compared to controls. Significantly increased expression of proinflammatory cytokines was also determined in UC and IBS-D as compared to controls. Hence we conclude that insufficient level of GABA in UC and IBS-D leads to overproduction of proinflammatory cytokines which further contributes to inflammation. GABA may be used as a promising therapeutic target for treatment of gut inflammation or other inflammatory diseases.

Keywords: diarrheal predominant irritable bowel syndrome, γ-aminobutyric acid (GABA), inflammation, ulcerative colitis

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Authors: Mohadese Hashemi, Elham Akhoundi Kharanaghi, Fatemeh Haghiralsadat, Mojgan Yazdani, Omid Javani, Mahboobe Sharafodini, Davood Rajabi

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Niosomes are non-ionic surfactant vesicles in aqueous media resulting in closed bilayer structures that can be used as carriers of hydrophilic and hydrophobic compounds. The use of niosomes for encapsulation of essential oils (EOs) is an attractive new approach to overcome their physicochemical stability concerns include sensibility to oxygen, light, temperature, and volatility, and their reduced bioavailability which is due to low solubility in water. EOs are unstable and fragile volatile compounds which have strong interest in pharmaceutical due to their medicinal properties such as antiviral, anti-inflammatory, antifungal, and antioxidant activities without side effects. Trachyspermum copticum (ajwain) is an annual aromatic plant with important medicinal properties that grows widely around Mediterranean region and south-west Asian countries. The major components of the ajwain oil were reported as thymol, γ-terpinene, p-cymene, and carvacrol which provide antimicrobial and antioxidant activity. The aim of this work was to formulate ajwain essential oil-loaded niosomes to improve water solubility of natural product and evaluate its physico-chemical features and stability. Ajwain oil was obtained through steam distillation using a clevenger-type apparatus and GC/MS was applied to identify the main components of the essential oil. Niosomes were prepared by using thin film hydration method and nanoparticles were characterized for particle size, dispersity index, zeta potential, encapsulation efficiency, in vitro release, and morphology.

Keywords: trachyspermum copticum, ajwain, niosome, essential oil, encapsulation

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Authors: Tella Toluwani, Adegbegi Ademuyiwa, Musei Chiedu, Adekunle Odola, Ayangbenro Ayansina, Adaramoye Oluwatosin

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Dithiocarbamates are very useful biological agents with antioxidant properties. Diclofenac (DIC) is a non-steroidal analgesic, anti-inflammatory, and antipyretic agent. The use of diclofenac has been linked with reproductive toxicity/damage. The purpose of this study is (i) To investigate the therapeutic potential of diisopropyldithiocarbamate sodium salt (Na(i-Pr₂dtc)) and vitamin E (VIT E) against diclofenac induced toxicity in the testes of male Wistar rats. (ii) To investigate the effect of (Na(i-Pr₂dtc)) and vitamin E on ameliorating damage done to the testes through histological analysis of the testes. Thirty-six (36) male Wistar rats were used for the experiment, they were divided into six (6) groups, the animals in group 1 served as control, animals in groups 2, 3, 4, 5 and 6 received DIC only, DIC and (Na(i-Pr₂dtc)), DIC and VIT E, (Na(i-Pr₂dtc) only and VIT E only respectively. A single dose of 100 mg/kg body weight of DIC was administered to male Wistar rats, while 30 mg/kg body weight of (Na(i-Pr₂dtc)) was used to treat both normal and DIC treated animals, control animals were treated with the vehicle, after 24 hrs of treatment the animals were euthanized and the testes were removed for analysis. The treatment of rats with Na(i-Pr₂dtc) significantly restored catalase (CAT) activity depressed by diclofenac. (Na(i-Pr₂dtc)) also restored glutathione levels reduced by DIC treatment and this was also accompanied by reduced lipid peroxidation (LPO) level. VIT E significantly restored superoxide dismutase (SOD) activity when compared with DIC only treated animals. Photomicrographs of testes from (Na(i-Pr₂dtc)) treated rats showed seminiferous epithelium with no lesions. We conclude that (Na(i-Pr₂dtc)) has an antioxidant effect, which might be related to the dose and duration of administration.

Keywords: diisopropyldithiocarbamate sodium salt, diclofenac, vitamin E, testes

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Authors: Yi-Hui Lai, Chih-Hsiang Yang, Li-Chung Hsu

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The inflammasome is a protein complex that modulates caspase-1 activity, resulting in proteolytic cleavage of proinflammatory cytokines such as IL-1β and IL-18, into their bioactive forms. It has been shown that the inflammasomes play a crucial role in the clearance of pathogenic infection and tissue repair. However, dysregulated inflammasome activation contributes to a wide range of human diseases such as cancers and auto-inflammatory diseases. Yet, regulation of NLRP3 inflammasome activation remains largely unknown. We discovered a novel DEAD box protein, whose biological function has not been reported, not only negatively regulates NLRP3 inflammasome activation by interfering NLRP3 inflammasome assembly and cellular localization but also mitigate pyroptosis upon pathogen evasion. The DEAD-box protein is the first DEAD-box protein gets involved in modulation of the inflammasome activation. In our study, we found that caspase-1 activation and mature IL-1β production were largely enhanced upon LPS challenge in the DEAD box-containing protein- deleted THP-1 macrophages and bone marrow-derived macrophages (BMDMs). In addition, this DEAD box-containing protein migrates from the nucleus to the cytoplasm upon LPS stimulation, which is required for its inhibitory role in NLRP3 inflammasome activation. The DEAD box-containing protein specifically interacted with the LRR motif of NLRP3 via its DEAD domain. Furthermore, due to the crucial role of the NLRP3 LRR domain in the recruitment of NLRP3 to mitochondria and binding to its adaptor ASC, we found that the interaction of NLRP3 and ASC was downregulated in the presence of the DEAD box-containing protein. In addition to the mechanical study, we also found that this DEAD box protein protects host cells from inflammasome-triggered cell death in response to broad-ranging pathogens such as Candida albicans, Streptococcus pneumoniae, etc., involved in nosocomial infections and severe fever shock. Collectively, our results suggest that this novel DEAD box molecule might be a key therapeutic strategy for various infectious diseases.

Keywords: inflammasome, inflammation, innate immunity, pyroptosis

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Authors: Swati Bhasin, Ali Ahmed, Valence Xavier, Ben Liu

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Aims: Diarrhea is a problem that is a frequent clinic referral to the gastroenterology and surgical team from the General practitioner. To establish a diagnosis, these patients undergo colonoscopy. The current practice at our district general hospital is to perform random left and right colonic biopsies. National guidelines issued by the British Society of Gastroenterology advise all patients presenting with chronic diarrhea should have an Ileoscopy as an indicator for colonoscopy completion. Our primary aim was to check if Terminal ileum (TI) biopsy is required to establish a diagnosis of inflammatory bowel disease (IBD). Methods: Data was collected retrospectively from November 2018 to November 2019. The target population were patients who underwent colonoscopies for diarrhea. Demographic data, endoscopic and histology findings of TI were assessed and analyzed. Results: 140 patients with a mean age of 57 years (19-84) underwent a colonoscopy (M: F; 1:2.3). 92 patients had random colonic biopsies taken and based on the histological results of these, 15 patients (16%) were diagnosed with IBD. The TI was successfully intubated in 40 patients, of which 32 patients had colonic biopsies taken as well. 8 patients did not have a colonic biopsy taken. Macroscopic abnormality in the TI was detected in 5 patients, all of whom were biopsied. Based on histological results of the biopsy, 3 patients (12%) were diagnosed with IBD. These 3 patients (100%) also had colonic biopsies taken simultaneously and showed inflammation. None of the patients had a diagnosis of IBD confirmed on TI intubation alone (where colonic biopsies were not done). None of the patients has a diagnosis of IBD confirmed on TI intubation alone (where colonic biopsies were negative). Conclusion: TI intubation is a highly-skilled, time-consuming procedure with a higher risk of perforation, which as per our study, has little additional diagnostic value in finding IBD for symptoms of diarrhea if colonic biopsies are taken. We propose that diarrhea is a colonic symptom; therefore, colonic biopsies are positive for inflammation if the diarrhea is secondary to IBD. We conclude that all of the IBDs can be diagnosed simply with colonic biopsies.

Keywords: biopsy, colon, IBD, terminal ileum

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Authors: Meltem Koray, Arda Ozgon, Duygu Ofluoglu, Mehmet Yaltirik

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Oral ulcerations can be seen as a side effect of different drugs. These ulcers usually appear within a few weeks following drug treatment. In most of cases, these ulcers resist to conventional treatments, such as anesthetics, antiseptics, anti-inflammatory agents, cauterization, topical tetracycline and corticosteroid treatment. The diagnosis is usually difficult, especially in patients receiving multiple drug therapies. Hyaluronan or hyaluronic acid (HA) is a biomaterial that has been introduced as an alternative approach to enhance wound healing and also used for oral ulcer treatment. The aim of this report is to present the treatment of drug-induced oral ulceration on maxillary mucosa with HA gel. 60-year-old male patient was referred to Department of Oral and Maxillofacial Surgery complaining of oral ulcerations during few weeks. He had received chemotherapy and radiotherapy in 2014 with the diagnosis of nasopharyngeal carcinoma, and he has accompanying systemic diseases such as; cardiological, neurological diseases and gout. He is medicated with Escitalopram (Cipralex® 20mg), Quetiapine (Seroquel® 100mg), Mirtazapine (Zestat® 15mg), Acetylsalicylic acid (Coraspin® 100mg), Ramipril-hydrochlorothiazide (Delix® 2.5mg), Theophylline anhydrous (Teokap Sr® 200mg), Colchicine (Colchicum Dispert® 0.5mg), Spironolactone (Aldactone® 100mg), Levothyroxine sodium (Levotiron® 50mg). He had painful oral ulceration on the right side of maxillary mucosa. The diagnosis was 'drug-induced oral ulceration' and HA oral gel (Aftamed® Oral gel) was prescribed 3 times a day for 2 weeks. Complete healing was achieved within 3 weeks without any side effect and discomfort. We suggest that HA oral gel is a potentially useful local drug which can be an alternative for management of drug-induced oral ulcerations.

Keywords: drug-induced, hyaluronic acid, oral ulceration, maxillary mucosa

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Authors: Tanveer Hussain, Misbah Hussain, Masroor Ellahi Babar, Muhammad Traiq Pervez, Fiaz Hussain, Sana Zahoor, Rashid Saif

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Interleukin 2 (IL-2) is a cytokine which is produced by activated T cells, play important role in immune response against antigen. It act in both autocrine and paracrine manner. It can stimulate B cells and various other phagocytic cells like monocytes, lymphokine-activated killer cells and natural killer cells. Acting in autocrine fashion, IL-2 protein plays a crucial role in proliferation of T cells. IL-2 triggers the release of pro and anti- inflammatory cytokines by activating several pathways. In present study, exon 1 of IL-2 gene of four local Pakistani breeds (Dera Din Panah, Beetal, Nachi and Kamori) from two provinces was amplified by using reported Ovine IL-2 primers, yielding PCR product of 501 bp. The sequencing of all samples was done to identify the polymorphisms in amplified region of IL-2 gene. Analysis of sequencing data resulted in identification of one novel nucleotide substitution (T→A) in amplified non-coding region of IL-2 gene. Comparison of IL-2 gene sequence of all four breeds with other goat breeds showed high similarity in sequence. While phylogenetic analysis of our local breeds with other mammals showed that IL-2 is a variable gene which has undergone many substitutions. This high substitution rate can be due to the decreased or increased changed selective pressure. These rapid changes can also lead to the change in function of immune system. This pioneering study of Pakistani goat breeds urge for further studies on immune system of each targeted breed for fully understanding the functional role of IL-2 in goat immunity.

Keywords: interleukin 2, mutational analysis, phylogeny, goat breeds, Pakistan

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Authors: Ankit Patil, Tushar D. Deshpande, Yogesh M. Nimdeo

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Pickering emulsions (PE) were developed in response to increased demand for organic, eco-friendly, and biocompatible products. These emulsions are usually stabilized by solid particles. In this research, we created chitosan-based sunflower oil-in-water (O/W) PE without the need for a surfactant. In our work, we employed chitosan, a biopolymer derived from chitin, as a stabilizer. This decision was influenced by chitosan's biocompatibility and biodegradability, as well as its anti-inflammatory and antibacterial capabilities. It also has other functional properties, such as antioxidant activity, a probiotic delivery mechanism, and the ability to encapsulate bioactive compounds. The purpose of this study was to govern key parameters that can be changed to obtain stable PE, such as the concentration of chitosan (0.3-0.5 wt.%), the concentration of oil (0.8-1 vol%), the pH of the emulsion (3-7) manipulated by the addition of 1M HCl/ 4M NaOH, and the amount of electrolyte (NaCl-0-300mM) added to increase or decrease ionic strength. A careful combination of these properties resulted in the production of the most stable and optimal PE. Particle size study found that emulsions with pH 6, 0.4% chitosan, and 300 mM salts were exceptionally stable, with droplet size 886 nm, PI of 0.1702, and zeta potential of 32.753.83 mV. It is fair to infer that when ionic strength rises, particle size, zeta potential, and PI value decrease. A lower PI value suggests that emulsion nanoparticles are more homogeneous. The addition of sodium chloride increases the ionic strength of the emulsion, facilitating the formation of more compact and ordered particle layers. These findings provide light on the creation of stimulus-responsive chitosan-based PE capable of encapsulating bioactive materials, functioning as antioxidants, and serving as food-grade emulsifiers.

Keywords: pickering emulsion, biocompatibility, eco-friendly, chitosan

Procedia PDF Downloads 238

Authors: Aneta Binkowska, Grzegorz Michalak, Slawomir Pilip, Lukasz Bondaruk, Daniel Celinski, Robert Slotwinski

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Post-traumatic mortality rates are still very high and show an increasing tendency. Early identification of patients at high risk of severe complications has a significant impact on treatment outcomes. The aim of the study was to better understand the early pathological inflammatory response to injury and infection and to determine the usefulness of the assessment of TNF-α and sTNFR1 concentrations in the peripheral blood as early indicators of severe post-traumatic complications. The study was carried out in a group of 51 patients after trauma treated in the ED, including 32 patients that met inclusion criteria for immunological analysis. Patients were divided into two groups using the ISS scale (group A with ISS ≥20, group B with ISS <20). Serum levels of TNF-α and sTNFR1 were determined after admission to the ED and after 3, 6, 12 and 24 hours. The highest TNF-α and sTNFR1 concentrations in both groups were recorded at admission and were significantly higher in group A compared to group B (A vs B TNF-α 2.46 pg/ml vs 1.78 pg/ml; sTNFR1 1667.5 pg/ml vs 875.2 p<0.005). The concentration of sTNFR1 in patients with severe complications was significantly higher compared to patients without complications and preceded clinical symptoms of complications ( C+ vs C- 1561.5 pg/ml vs 930.6 pg/ml). Spearman's correlation showed a statistically significant positive correlation between the baseline concentrations of IL-6 (r=0.38, p<0.043) and sTNFR1 (r=0.59, p=0.001) and the ISS scores. The high diagnostic sensitivity calculated from the ROC (receiver operating characteristic) curves was found for the concentrations of both cytokines: TNF α (AUC=0.91, p=0.004) and sTNFR1 (AUC=0.86, p=0.011). Elevated levels of sTNFR1, determined in the peripheral blood shortly after injury, is significantly associated with the occurrence of later complications, which in some patients lead to death. In contrast, high levels of TNF-α shortly after injury are associated with high mortality.

Keywords: cytokine, SIRS, MODS, trauma

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Authors: Sachin K. Samuchiwal, Barbara Balestrieri, Amanda Paskavitz, Hannah Raff, Joshua A. Boyce

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IL-33, a recently discovered member of the IL-1 cytokine family, binds to the TLR/IL1R super family receptor ST2 and induces type 2 immune responses. IL-33 is constitutively expressed in structural cells at barrier sites such as skin, lung, and intestine, and also inducibly expressed by hematopoietic cells including macrophages. Stimulation of macrophages by Lipopolysaccharide (LPS) can induce de novo IL-33 expression, and also causes the production of prostaglandin-E2 (PGE2) via cyclooxygenase (COX)-2 and microsomal PGE2 synthase-1 (mPGES-1). Because PGE2 can regulate macrophage functions through both autocrine and paracrine mechanisms, the potential interplay of endogenous PGE2 on IL-33 production was explored. Bone-marrow derived murine macrophages (bmMF) that lack either mPGES-1 or EP2 receptor expression were stimulated with LPS in the absence or presence of exogenous PGE2 along with pharmacological agonists and antagonists. The study results demonstrate that endogenous PGE2 markedly enhances LPS-induced IL-33 production by bmMFs via EP2 receptors. Moreover, exogenous PGE2 can amplify LPS-induced IL-33 expression dominantly by EP2 and partly by EP4 receptors by a pathway involving cAMP and exchange protein activated by cAMP (EPAC), but not protein kinase A (PKA). Though both IL-33 production and PGE2 generation in response to LPS require activation of both p38 MAPK and NF-κB, PGE2 did not influence this activation. In conclusion, it is demonstrated that endogenous PGE2 signaling through EP2 and EP4 receptors is a prerequisite for LPS-induced IL-33 production in bmMFs and the underlying cAMP mediated pathway involves EPAC. Since IL-33 is a critical pro-inflammatory cytokine in various pathological disorders, this PGE2-EP2/EP4-cAMP mediated pathway can be exploited to intervene in IL-33 driven pathologies.

Keywords: bone marrow macrophages, EPAC, IL-33, PGE2

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Authors: Dan Yan, Yunuo Zhang, Yuhan Huang, Weijie Ouyang

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The cornea serves as a vital protective barrier for the eye; however, it is prone to injury and damage that can disrupt corneal epithelium and nerves, triggering inflammation. Therefore, understanding the biological effects and molecular mechanisms involved in corneal wound healing and identifying drugs targeting these pathways is crucial for researchers in this field. This study aimed to investigate the therapeutic potential of progranulin (PGRN) in treating corneal injuries. Our findings demonstrated that PGRN significantly enhanced corneal wound repair by accelerating corneal re-epithelialization and re-innervation. In vitro experiments with cultured epithelial cells and trigeminal ganglion cells further revealed that PGRN stimulated corneal epithelial cell proliferation and promoted axon growth in trigeminal ganglion cells. Through RNA-sequencing (RNA-seq) analysis and other experimental techniques, we discovered that PGRN exerted its healing effects by modulating the Wnt signaling pathway, which played a critical role in repairing epithelial cells and promoting axon regeneration in trigeminal neurons. Importantly, our study highlighted the anti-inflammatory properties of PGRN by inhibiting the NF-κB signaling pathway, leading to decreased infiltration of macrophages. In conclusion, our findings underscored the potential of PGRN in facilitating corneal wound healing by promoting corneal epithelial cell proliferation, trigeminal ganglion cell axon regeneration, and suppressing ocular inflammation. These results suggest that PGRN could potentially expedite the healing process and improve visual outcomes in patients with corneal injuries.

Keywords: cornea, wound healing, progranulin, corneal epithelial cells, trigeminal ganglion cells

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Authors: Bassant M. M. Ibrahim, Doha H. Abou Baker, Ahmed Abd Elghafour

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Excessive exposure to heavy metals contributes to the occurrence of deleterious health problems that affect vital organs like the brain, liver, kidneys, and heart. The use of natural products that have antioxidant capabilities may contribute to the protection of these organs. In the present study, the essential oil of summer savory (Satureja hortensis) was used to evaluate its protective effects against lead acetate induced damaging effect on rats’ vital organs, due to its high contents of carvacrol, y-terpinene, and p-cymene. Forty female Wister Albino rats were classified into five equal groups, the 1st served as normal group, the 2nd served as positive control group was given lead acetate (60 mg/kg) intra-peritoneal (IP), the third to fifth groups were treated with calcium disodium (EDTA) as chelating agent and summer savory essential oil in doses of (50 and 100mg/kg) respectively. All treatments were given IP concomitant with lead acetate for ten successive days. At the end of the experiment duration electrocardiogram (ECG), an open field test for the evaluation of psychological state, rotarod test as for the evaluation of locomotor coordination ability as well as anti-inflammatory and oxidative stress biomarkers in serum and histopathology of vital organs were performed. The investigations in this study show that the protective effect of high dose of summer savory essential oil is more than the low dose and that the essential oil of summer savory is a promising agent that can contribute to the protection of vital organs against the hazardous damaging effects of lead acetate.

Keywords: brain, heart, kidneys, lead acetate, liver, protective, summer savory

Procedia PDF Downloads 123

Authors: Sri Suparwitri

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When an orthodontic force is applied to a tooth, an inflammatory response is initiated then lead to bone remodeling process, and the process accommodates tooth movement. One of cytokine that plays a prominent role in bone remodeling process was transforming growth factor-beta 1 (TGF-β1). The purpose of this study was to identify and compare changes of TGF-β1 in human gingival crevicular fluid during canine retraction using elastic chain and closed coil spring. Ten patients (mean age 20.7 ± 2.9 years) participated. The patients were entering the space closure phase of fixed orthodontic treatment. An upper canine of each patient was retracted using elastic chain, and the contralateral canine was retracted using closed coil spring. Gingival crevicular fluid samples were collected from the canine teeth before and 7 days after the force was applied. Transforming growth factor-beta 1 was determined by enzyme-linked immunosorbent assay (ELISA). The concentrations of TGF-β1 at 7 days were significantly higher compared to before canine retraction in both groups. In the evaluation of between-group difference, before retraction, the difference was insignificant, whereas at 7 days significantly higher values were determined in the closed coil spring group compared to elastic chain group. The result suggests that TGF-β1 is associated with the bone remodeling that occurs during canine distalization movement. Closed coil spring gave higher TGF-β1 concentrations thus more bone remodeling occurred and may be considered the treatment of choice.

Keywords: closed coil spring, elastic chain, gingival crevicular fluid, TGF-β1

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Authors: Arslan Masood Pirzada, Muhammad Naeem, Hafiz Haider Ali, Muhammad Latif, Aown Sammar Raza, Asad Hussain Bukhari, Muhammad Saqib, Muhammad Ijaz

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Cyperus rotundus (Cyperaceae), a medicinal herb, is being traditionally used as a home remedy for the treatment of various clinical conditions like diarrhea, diabetic, pyretic, inflammation, malaria, and for treating stomach and bowel disorders. Its current status is one of the most widespread, troublesome, and economically damaging agronomic weeds, growing wildly in various tropical and sub-tropical regions of the world. Tuber and rhizomes of Cyperus rotundus possess a higher concentration of active ingredients in the form of essential oils, phenolic acids, ascorbic acids and flavonoids, responsible for its remedial properties. Exploitation of any medicinal plant application depends on the crucial and comprehensive information about the therapeutic potential of a plant. Researchers have evaluated and characterized the significance of Cyperus rotundus as an anti-androgenic, anti-bacterial, anti-cancerous, anti-convulsant, anti-diabetic, anti-diarrheal, anti-genotoxic, anti-inflammatory, anti-lipidemic, anti-malarial, anti-mutagenic, anti-obesity, anti-oxidant, anti-uropathogenic, hepato-, cardio-, neuroprotective, and nootropic agent. This paper comprises a broad review to summarize the current state of knowledge about chemical constituents, potential economic uses and therapeutic aspects of Cyperus rotundus that will aid in the development of bioethanol and modern herbal medicine through latest technologies that will promote the ability of this plant in the cure of many clinical disorders.

Keywords: purple nutsedge, chemical composition, economic uses, therapeutic values, future directions

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Authors: Khushbu Priyadarshi, Chandramani Pathak

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Cancer cells can develop resistance to conventional therapies especially chemotherapeutic drugs. Resistance to chemotherapy is another challenge in cancer therapeutics. Therefore, it is important to address this issue. Gallic acid (GA) is a natural plant compound that exhibits various biological properties including anti-proliferative, anti-inflammatory, anti-oxidant and anti-bacterial. Despite of the wide spectrum biological properties GA has cytotoxic response and low bioavailability. To overcome this problem, GA was conjugated with the Polyamidoamine(PAMAM) dendrimer for improving the bioavailability and efficient delivery in drug-resistant HCT-116 Colon Cancer cells. Gallic acid was covalently linked to 4.0 G PAMAM dendrimer. PAMAM dendrimer is well established nanocarrier but has cytotoxicity due to presence of amphiphilic nature of amino group. In our study we have modified surface of PAMAM dendrimer with Gallic acid and examine their anti-proliferative effects in drug-resistant HCT-116 cells. Further, drug-resistant colon cancer cells were established and thereafter treated with different concentration of PAMAM-GA to examine their anti-proliferative potential. Our results show that PAMAM-GA conjugate induces apoptotic cell death in HCT-116 and drug-resistant cells observed by Annexin-PI staining. In addition, it also shows that multidrug-resistant drug transporter P-gp protein expression was downregulated with increasing the concentration of GA conjugate. After that we also observed the significant difference in Rh123 efflux and accumulation in drug sensitive and drug-resistant cancer cells. Thus, our study suggests that conjugation of anti-cancer agents with PAMAM could improve drug resistant property and cytotoxic response to treatment of cancer.

Keywords: drug resistance, gallic acid, PAMAM dendrimer, P-glycoprotein

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Authors: Ouzid Yasmina, Aiche-Iratni Ghenima, Harchaoui Lina, Saadoun Noria, Houali Karim

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Medicinal plants are an important source of bioactive molecules with biological activities such as anticancer, antioxidant, anti-inflammatory, antibacterial, antimitotic.... These molecules include alkaloids, polyphenols and terpenes. The latter can be extracted by different solvents, namely: water, ethanol, methanol, butanol, acetone... This is why it seemed interesting to us to evaluate in vitro the antimitotic and genotoxic effect of these secondary metabolites contained in the aqueous extract of the leaves of Peganum harmala L. by the Allium cepa L. test on meristematic cells by calculating the mitotic parameters (The mitotic index, the aberration index and the limit value of cytotoxicity).A spectrophotometric determination of secondary metabolites, namely alkaloids and flavonoids in the aqueous extract of this essence, was performed. As a result, the alkaloid content is estimated to be 28.42 μg EC/mg extract, and the flavonoid content is 12.52 μg EQ/mg extract. The determination of the mitotic index revealed disturbances in cell division with a highly significant difference between the negative control (distilled water) and the different samples (aqueous extracts, colchicine and quecetin). The exposure of meristematic cells to our samples resulted in a large number of chromosomal, nuclear and cellular aberrations with an aberration index reaching 16.21±1.28% for the 4mg/ml aqueous extract and 11.71±3.32% for the 10mg/ml aqueous extract. The limit value of cytotoxicity revealed that our samples are sublethal on Allium cepa L. meristematic cells.

Keywords: allium cepa l., antimitotic and genotoxic effect, aqueous leaf extract, laghouat (algeria), peganum harmala l., secondary metabolites

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