Search results for: obese mice

Authors: S. Essa, H. Safar, R. Raghupathy

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Human cytomegalovirus (CMV) continues to be a source of severe complications to immunologically immature and immune-compromised hosts. Effective CMV vaccine that diminishes CMV disease in transplant patients and avoids congenital infection remains of high importance as no approved vaccines exist. Though the exact links of defense mechanisms are unidentified, viral-specific antibodies and Th1/Th2 cytokine responses have been involved in controlling viral infections. CMV envelope glycoprotein B (UL55/gB), the matrix proteins (UL83/pp65, UL99/pp28, UL32/pp150), and the assembly protein UL80a/pp38 are known to be targets of antiviral immune responses. In this study, mice were immunized with five HCMV antigens (UL32/pp150, UL80a/pp38, UL99/pp28, and UL83/pp65), and serum samples were collected and evaluated for eliciting viral-specific antibody responses. Moreover, Splenocytes were collected, stimulated, and assessed for cytokine responses. The results demonstrated a CMV-antigen-specific antibody response to pp38 and pp65 (E/C >2.0). The highest titers were detected with pp38 (average E/C 16.275) followed by pp65 (average E/C 7.72). Compared to control cells, splenocytes from PP38 antigen immunized mice gave a significantly higher concentration of GM-CSF, IFN-γ, IL-2 IL-4, IL-5, and IL-17A (P<0.05). Also, splenocytes from pp65 antigen immunized mice resulted in a significantly higher concentration of GM-CSF, IFN-γ, IL-2 IL-4, IL-10, IL-12, IL-17A, and TNF- α. The designation of target CMV peptides by identifying viral-specific antibodies and cytokine responses is vital for understanding the protective immune mechanisms during CMV infection and identifying appropriate viral antigens to develop novel vaccines.

Keywords: hepatitis C virus, peripheral blood mononuclear cells, neutrophils, cytokines

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Authors: Santram Lodhi, Alok Pal Jain, Awesh K. Yadav, Gopal Rai

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Rhodiola rosea L. (Crassulaceae) is commonly known as golden root or rose root. It is a perennial herbaceous plant and most investigated species of the genus Rhodiola. Rhodiola rosea contains flavonoids, terpenoids, phenylpropanoid glycosides and phenylethanol derivatives in the roots of the plant. The objective of present study was to investigate the protective effect of hydroalcoholic extract from Rhodiola rosea roots in DSS induced colitis in mice. The ulcerative colitis was induced by DSS (3%, w/v) in mice and estimated weight loss and stool consistency. Various parameters including Colon length, spleen weights and ulcer index were also measured. The histological observations were observed by H&E staining. Effect of hydroalcoholic extract on various antioxidant parameter of rat colon such as tissue myeloperoxidase (MPO), reduced GSH, SOD concentrations and lipid peroxidation were determined. Pro-inflammatory mediators, such as tumour necrosis factor-α (TNF-α) and nitric oxide (NO) were determined by ELISA. In DSS induced group, mice body weight decreased gradually as compared to the control group. Redness and edema were observed in the colons intensely and scores representing inflammation in this group. The extract treated showed with tissue levels of TNF-α, IL-6 and MPO activity were significantly (p<0.05) increased. The mice treated with higher doses of hydroalcoholic extract (300 mg/kg) significantly reduced the activity compared with standard drug sulfasalazine (100 mg/kg. B.wt). Conclusion: Results of this study were suggested that the efficacy of hydroalcoholic extract, especially at the higher dose, was similar to that of standard drug, which concerned its potential application as a natural medicine for the treatment of ulcerative colitis.

Keywords: phenylpropanoid, Rhodiola rosea, sulfasalazin, ulcerative colitis

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Authors: Suparmi, Israhnanto Isradji, Dina Fatmawati, Iwang Yusuf

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Kepel (Stelechocarpus burahol) is one of the traditional plants originating from Indonesia that can be used to prevent pregnancy, launched urine and kidney inflammation. Kepel pulp has compounds alkaloid, triterpenoid, tannin, saponin, and flavonoid, when used will give the hormonal and cytotoxic effect. This study was aimed at evaluating ethanol extract of kepel in vivo for anti-implantation activities. In this experimental study with post test only control group design, 20 female mice were randomly divided into 4 groups. It was divided into the control, the 0,65 mg dose, 1,3 mg dose, and 3,6 mg dose of kepel pulp extract group. The extract soluted in DMSO’s solution and was given 1 ml per mice. The extract was given 10 days before copulation until 18 days of pregnancy. Then, the number of implantation, presence of fetus, and embrio resorbtion were recorded and used to calculate the percentage anti-implantation effect. The results were tested by One-way ANOVA. The mean number of implantation in group control, 0,65 mg;1,3 mg; and 2,6 mg were 5,60±1,14; 6,20± 1,64; 7,60±1,51; 8,00± 1,58, respectively. One way Annova test showed that there is no significant difference in the number of implantation between the group (p > 0,05). The administration of kepel pulp ethanol extract had no effect on the percentage anti-implantation effect and the number of and embrio resorbtion.

Keywords: antiimplantation, fetus, Stelechocarpus burahol, flavonoid

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Authors: Makan Cheraghpour, Seyed Ahmad Hosseini, Damoon Ashtary-Larky, Saeed Shirali, Matin Ghanavati, Meysam Alipour

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Background: In addition to reducing body weight, the low-calorie diets can reduce the lean body mass. It is hypothesized that in addition to reducing the body weight, the low-calorie diets can maintain the lean body mass. So, the current study aimed at evaluating the effects of high-protein diet with calorie restriction on body composition in overweight and obese individuals. Methods: 36 obese and overweight subjects were divided randomly into two groups. The first group received a normal-protein, low-energy diet (RDA), and the second group received a high-protein, low-energy diet (2×RDA). The anthropometric indices including height, weight, body mass index, body fat mass, fat free mass, and body fat percentage were evaluated before and after the study. Results: A significant reduction was observed in anthropometric indices in both groups (high-protein, low-energy diets and normal-protein, low-energy diets). In addition, more reduction in fat free mass was observed in the normal-protein, low-energy diet group compared to the high -protein, low-energy diet group. In other the anthropometric indices, significant differences were not observed between the two groups. Conclusion: Independently of the type of diet, low-calorie diet can improve the anthropometric indices, but during a weight loss, high-protein diet can help the fat free mass to be maintained.

Keywords: diet, high-protein, body mass index, body fat percentage

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Authors: Zi-Han Li, Lu Fang, Liang Wu, Dong-Yuan Chang, Manyuan Dong, Liang Ji, Qi Zhang, Ming-Hui Zhao, Sydney C. W. Tang, Lemin Zheng, Min Chen

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Uncoupling of mitochondrial respiration by chemical uncouplers has proven effective in ameliorating obesity, insulin resistance, and hyperglycemia, which were risk factors for diabetic nephropathy (DN). Recently, we found that ANXA1 could improve mitochondrial function to mitigate DN progression. However, the underlying mechanism is not fully clear yet. Here, we identified uncoupling protein 1 (UCP1), an inner membrane protein of mitochondria, as a key to mitochondrial homeostasis improved by ANXA1. Specifically, ANXA1 attenuated mitochondrial dysfunction via appropriately upregulating UCP1 by stabilizing its transcription factor GATA binding protein 3 (GATA3) by combining it with thioredoxin. Moreover, specific overexpression of UCP1 in the renal cortex rescued renal injuries in diabetic Anxa1-KO mice. UCP1 deletion aggravated renal injuries in HFD/STZ-induced diabetic mice. Mechanistically, UCP1 reduced mitochondrial fission through the aristaless-related homeobox (ARX)/cardiolipin synthase 1 (CRLS1) pathway. Therapeutically, CL316243, a UCP1 agonist, could attenuate established DN in db/db mice. This work established an alternative principle to harness the power of uncouplers for the treatment of DN.

Keywords: diabetic nephropathy, uncoupling protein 1, mitochondrial homeostasis, cardiolipin metabolism

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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: Fui Ping Lim, Wen Choong Chua, Toan Thang Phan

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Aim: This study investigates the roles of Cord Lining Stem Cells (CLSCs) as potential therapeutic agents for diabetic wounds. Method: 20 genetically diabetic db/db mice were randomly assigned to two arms; (i) control group received placebo treatment (sham media or cells delivery material), and (ii) active comparator received CLSCs. Two full-thickness wounds, each sized 10mm X 10mm were created, one on each side of the midline on the back of the mice. Digital pictures were taken on day 1, 3, 7, 10, 14, 17, 21, 24, 28. Wound areas were analyzed with ImageJ TM software and calculated as percentage of the original wound. Time to closure was defined as the day the wound bed was completely epithelized and filled with new tissues. Results: The CLSCs-treated wounds, showed a significant increase in the percentage of wound closure and achieved 100% closure of the wound sooner than the control group by an average of 3.7 days. The mice treated with CLSCs have a shorter wound closure time (mean closure day: 19.8 days) as compared to the control group (mean closure day: 23.5 days). Conclusion: Our preliminary findings inferred that CLSCs treated wound achieved higher percentage of wound closure within a shorter duration of time.

Keywords: cord lining stem cell, diabetic wound, stem cell, wound

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Authors: Zi-Han Li, Lu Fang, Liang Wu, Dong-Yuan Chang, Manyuan Dong, Liang Ji, Qi Zhang, Ming-Hui Zhao, Sydney C.W. Tang, Lemin Zheng, Min Chen

Abstract:

Uncoupling of mitochondrial respiration by chemical uncouplers has proven effective in ameliorating obesity, insulin resistance, and hyperglycemia, which were risk factors for diabetic nephropathy (DN). Recently, it was found that annexin A1(ANXA1) could improve mitochondrial function to mitigate DN progression. However, the underlying mechanism is not fully clear yet. Here, it was identified that uncoupling protein 1 (UCP1), an inner membrane protein of mitochondria, as a key to mitochondrial homeostasis improved by ANXA1. Specifically, ANXA1 attenuated mitochondrial dysfunction via appropriately upregulating UCP1 by stabilizing its transcription factor GATA binding protein 3 (GATA3) through combining with thioredoxin. Moreover, specific overexpression of UCP1 in renal cortex rescued renal injuries in diabetic Anxa1-KO mice. UCP1 deletion aggravated renal injuries in HFD/STZ-induced diabetic mice. Mechanistically, UCP1 reduced mitochondrial fission through the aristaless-related homeobox (ARX)/cardiolipin synthase 1 (CRLS1) pathway. Therapeutically, CL316243, a UCP1 agonist, could attenuate established DN in db/db mice. This work established a novel principle to harness the power of uncouplers for the treatment of DN.

Keywords: diabetic nephropathy, uncoupling protein 1, mitochondrial homeostasis, cardiolipin metabolism

Procedia PDF Downloads 54

Authors: Irina M. Kolesnikova, Andrey M. Gaponov, Sergey A. Roumiantsev, Tatiana V. Grigoryeva, Alexander V. Laikov, Alexander V. Shestopalov

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Background. Neuropathy is a common complication of obesity. In this regard, the content of neurotrophins in such patients is of particular interest. Neurotrophins are the proteins that regulate neuron survival and neuroplasticity and include brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). However, the risk of complications depends on the metabolic type of obesity. Metabolically unhealthy obesity (MUHO) is associated with a high risk of complications, while this is not the case with metabolically healthy obesity (MHO). Therefore, the aim of our work was to study the effect of the obesity metabolic type on serum neurotrophins levels. Patients, materials, methods. The study included 134 healthy donors and 104 obese patients. Depending on the metabolic type of obesity, the obese patients were divided into subgroups with MHO (n=40) and MUHO (n=55). In the blood serum, the concentration of BDNF and NGF was determined. In addition, the content of adipokines (leptin, asprosin, resistin, adiponectin), myokines (irisin, myostatin, osteocrin), indicators of carbohydrate, and lipid metabolism were measured. Correlation analysis revealed the relationship between the studied parameters. Results. We found that serum BDNF concentration was not different between obese patients and healthy donors, regardless of obesity metabolic type. At the same time, in obese patients, there was a decrease in serum NGF level versus control. A similar trend was characteristic of both MHO and MUHO. However, MUHO patients had a higher NGF level than MHO patients. The literature indicates that obesity is associated with an increase in the plasma concentration of NGF. It can be assumed that in obesity, there is a violation of NGF storage in platelets, which accelerates neurotrophin degradation. We found that BDNF concentration correlated with irisin levels in MUHO patients. Healthy donors had a weak association between NGF and VEGF levels. No such association was found in obese patients, but there was an association between NGF and leptin concentrations. In MHO, the concentration of NHF correlated with the content of leptin, irisin, osteocrin, insulin, and the HOMA-IR index. But in MUHO patients, we found only the relationship between NGF and adipokines (leptin, asprosin). It can be assumed that in patients with MHO, the replenishment of serum NGF occurs under the influence of muscle and adipose tissue. In the MUHO patients only the effect of adipose tissue on NGF was observed. Conclusion. Obesity, regardless of metabolic type, is associated with a decrease in serum NGF concentration. We showed that muscle and adipose tissues make a significant contribution to the serum NGF pool in the MHO patients. In MUHO there is no effect of muscle on the NGF level, but the effect of adipose tissue remains.

Keywords: neurotrophins, nerve growth factor, NGF, brain-derived neurotrophic factor, BDNF, obesity, metabolically healthy obesity, metabolically unhealthy obesity

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Authors: O. M. Alabi, F. A. Aderemi, M. O. Ayoola

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An aspect of biosecurity measures to ensure good welfare for chickens is rodents’ control. Rats and mice are rodents commonly found in poultry houses in most of the African countries. More than 20,000 species of rat have been identified in Africa among which are; Black house rats (Rattus rattus), East African mole rat (Tachyorcytes splendens), Naked mole rat (Heterocephalus glaber), Zambian mole rat (Fukomys mechowii), African grass rat (Arvicanthis niloticus), Nigerian mole rat (Cryptomys foxi), Target rat (Stochomys longicaudatus) and West African Shaggy rat (Dasymis rufulus). Apart from being destructive, rats and mice are voracious in that they compete with chickens for feed and water thereby causing economical losses to the farmer, they are also vectors to many pathogens of poultry diseases such as Salmonellosis, colibacillosis, ascaridiasis, coryza, pasteurellosis and mycoplasmosis. As bad as these rodents are to the poultry farmers, they are good sources of animal protein to local hunters and other farmers in most African countries. Rat is considered a delicacy in Nigeria and many other African countries hence the need to investigate into how the rats species will not go into extinction. Rodents are usually controlled by poultry farmers with the use of rodenticides which can either be anticoagulant or stomach poison, and with the use of baits. However, elimination of rats and mice is being considered as callous act against these species of animal and their natural existence as human food also. This paper therefore suggests that sanitation methods such as feed removal from rats and mice, controlling feed and water spillage, proper disposal of waste eggs, dead birds and garbage, keeping the surroundings of the poultry clean; rodent proofing by making it difficult for rodents to enter the poultry houses are some of the humane ways of controlling rodents in poultry production to avoid improving the welfare of a particular animal at the expense of the other.

Keywords: management, poultry, rodents, welfare

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

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

Keywords: naringenin, in vitro, cell line, anticancer

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Authors: Nicolas Galazis, Nikolina Docheva, Constantinos Simillis, Kypros Nicolaides

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Background: Obese women are at increased risk for many pregnancy complications, and bariatric surgery (BS) before pregnancy has shown to improve some of these. Objectives: To review the current literature and quantitatively assess the obstetric and neonatal outcomes in pregnant women who have undergone BS. Search Strategy: MEDLINE, EMBASE and Cochrane databases were searched using relevant keywords to identify studies that reported on pregnancy outcomes after BS. Selection Criteria: Pregnancy outcome in firstly, women after BS compared to obese or BMI-matched women with no BS and secondly, women after BS compared to the same or different women before BS. Only observational studies were included. Data Collection and Analysis: Two investigators independently collected data on study characteristics and outcome measures of interest. These were analysed using the random effects model. Heterogeneity was assessed and sensitivity analysis was performed to account for publication bias. Main Results: The entry criteria were fulfilled by 17 non-randomised cohort or case-control studies, including seven with high methodological quality scores. In the BS group, compared to controls, there was a lower incidence of preeclampsia (OR, 0.45, 95% CI, 0.25-0.80; p=0.007), GDM (OR, 0.47, 95% CI, 0.40-0.56; P<0.001) and large neonates (OR 0.46, 95% CI 0.34-0.62; p<0.001) and a higher incidence of small neonates (OR 1.93, 95% CI 1.52-2.44; p<0.001), preterm birth (OR 1.31, 95% CI 1.08-1.58; p=0.006), admission for neonatal intensive care (OR 1.33, 95% CI 1.02-1.72; p=0.03) and maternal anaemia (OR 3.41, 95% CI 1.56-7.44, p=0.002). Conclusions: BS as a whole improves some pregnancy outcomes. Laparoscopic adjustable gastric banding does not appear to increase the rate of small neonates that was seen with other BS procedures. Obese women of childbearing age undergoing BS need to be aware of these outcomes.

Keywords: bariatric surgery, pregnancy, preeclampsia, gestational diabetes, birth weight

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Authors: Patcharapa Thaweekul, Paskorn Sritipsukho

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Background: During the training period of the 6-year medical curriculum, medical students seem to have many risk behaviors of developing obesity. This study aims to demonstrate the prevalence and risk behavior of obesity and related metabolic disorders among the final-year medical students of Thammasat University as well as the change in nutritional status during studying program. Methods: 123 participants were asked to complete the self-report questionnaires. Weight, height, waist circumference and blood pressure were obtained. Blood samples were drawn for total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides and plasma glucose. Body weight and height of the medical students in the first year were obtained from the medical report at the entry. Results: The prevalence of overweight and obesity at the entry to medical school was 22.0% and increased to 30.1% in the final year. Two obese students (5.4%) was diagnosed as metabolic syndrome. During 6-year curriculum, the BMI gained in male medical students were more significant as compared to female students (1.76±1.74 and 0.43±1.82 kg/m2, respectively; p <.001). The current BMI is significantly correlated with the BMI at entry. Serum LDL-C in the overweight/obese students was significantly higher as compared to the normal weight and underweight group. Sleep deprivation was a significantly frequent behavior in the overweight/obese students. Conclusion: Medical students, as having high-risk behaviors, should be assessed for the nutritional status and metabolic parameters. Medical schools should promote the healthy behaviors to increase the healthy eating and exercise habits and reduced the risk behaviors among them.

Keywords: medical students, metabolic syndrome, obesity, risk behaviors

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Authors: Samia A. El-Fiky, F. A. Abou-Zaid, Ibrahim M. Farag, Naira M. Efiky

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Clomipramine hydrochloride is one of the most used tricyclic antidepressant drug in Egypt. This drug contains in its chemical structure on two benzene rings. Benzene is considered to be toxic and clastogenic agent. So, the present study was designed to assess the genotoxic effect of Clomipramine hydrochloride on somatic and germ cells in mice. Three dose levels 0.195 (Low), 0.26 (Medium), and 0.65 (High) mg/kg.b.wt. were used. Seven groups of male mice were utilized in this work. The first group was employed as a control. In the remaining six groups, each of the above doses was orally administrated for two groups, one of them was treated for 5 days and the other group was given the same dose for 30 days. At the end of experiments, the animals were sacrificed for cytogenetic and sperm examination as well as histopathological investigations by using hematoxylin and eosin stains (H and E stains) and electron microscope. Concerning the sperm studies, these studies were confined to 5 days treatment with different dose levels. Moreover, the ultrastructural investigation by electron microscope was restricted to 30 days treatment with drug doses. The results of the dose dependent effect of Clomipramine showed that the treatment with three different doses induced increases of frequencies of chromosome aberrations in bone marrow and spermatocyte cells as compared to control. In addition, mitotic and meiotic activities of somatic and germ cells were declined. The treatments with medium or high doses were more effective for inducing significant increases of chromosome aberrations and significant decreases of cell divisions than treatment with low dose. The effect of high dose was more pronounced for causing such genetic deleterious in respect to effect of medium dose. Moreover, the results of the time dependent effect of Clomipramine observed that the treatment with different dose levels for 30 days led to significant increases of genetic aberrations than treatment for 5 days. Sperm examinations revealed that the treatment with Clomipramine at different dose levels caused significant increase of sperm shape abnormalities and significant decrease in sperm count as compared to control. The adverse effects on sperm shape and count were more obviousness by using the treatments with medium or high doses than those found in treatment with low dose. The group of mice treated with high dose had the highest rate of sperm shape abnormalities and the lowest proportion of sperm count as compared to mice received medium dose. In histopathological investigation, hematoxylin and eosin stains showed that, the using of low dose of Clomipramine for 5 or 30 days caused a little pathological changes in liver tissue. However, using medium and high doses for 5 or 30 days induced severe damages than that observed in mice treated with low dose. The treatment with high dose for 30 days gave the worst results of pathological changes in hepatic cells. Moreover, ultrastructure examination revealed, the mice treated with low dose of Clomipramine had little differences in liver histological architecture as compared to control group. These differences were confined to cytoplasmic inclusions. Whereas, prominent pathological changes in nuclei as well as dilated of rough Endoplasmic Reticulum (rER) were observed in mice treated with medium or high doses of Clomipramine drug. In conclusion, the present study adds evidence that treatments with medium or high doses of Clomipramine have genotoxic effects on somatic and germ cells of mice, as unwanted side effects. However, the using of low dose (especially for short time, 5 days) can be utilized as a therapeutic dose, where it caused relatively similar proportions of genetic, sperm, and histopathological changes as those found in normal control.

Keywords: clomipramine, mice, chromosome aberrations, sperm abnormalities, histopathology

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Authors: Yi Li, Yinan Zheng, Ya Ke, Yungwing Ho

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Motor learning is a process that frequently happens among humans and rodents, which is defined as the changes in the capability to perform a skill that is conformed to have a relatively permanent improvement through practice or experience. There are many ways to learn a behavior, among which is observational learning. Observational learning is the process of learning by watching the behaviors of others, for example, a child imitating parents, learning a new sport by watching the training videos or solving puzzles by watching the solutions. Many research explores observational learning in humans and primates. However, the neuronal mechanism of which, especially observational motor learning, was uncertain. It’s well accepted that mirror neurons are essential in the observational learning process. These neurons fire when the primate performs a goal-directed action and sees someone else demonstrating the same action, which suggests they have high firing activity both completing and watching the behavior. The mirror neurons are assumed to mediate imitation or play a critical and fundamental role in action understanding. They are distributed in many brain areas of primates, i.e., posterior parietal cortex (PPC), premotor cortex (M2), and primary motor cortex (M1) of the macaque brain. However, few researchers report the existence of mirror neurons in rodents. To verify the existence of mirror neurons and the possible role in motor learning in rodents, we performed customised string-pulling behavior combined with multiple behavior analysis methods, photometry, electrophysiology recording, c-fos staining and optogenetics in healthy mice. After five days of training, the demonstrator (demo) mice showed a significantly quicker response and shorter time to reach the string; fast, steady and accurate performance to pull down the string; and more precisely grasping the beads. During three days of observation, the mice showed more facial motions when the demo mice performed behaviors. On the first training day, the observer reduced the number of trials to find and pull the string. However, the time to find beads and pull down string were unchanged in the successful attempts on the first day and other training days, which indicated successful action understanding but failed motor learning through observation in mice. After observation, the post-hoc staining revealed that the c-fos expression was increased in the cognitive-related brain areas (medial prefrontal cortex) and motor cortices (M1, M2). In conclusion, this project indicated that the observation led to a better understanding of behaviors and activated the cognitive and motor-related brain areas, which suggested the possible existence of mirror neurons in these brain areas.

Keywords: observation, motor learning, string-pulling behavior, prefrontal cortex, motor cortex, cognitive

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Authors: Irina M. Kolesnikova, Andrey M. Gaponov, Sergey A. Roumiantsev, Tatiana V. Grigoryeva, Dilyara R. Khusnutdinova, Dilyara R. Kamaldinova, Alexander V. Shestopalov

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Background. Obese patients have unequal risks of metabolic disorders. It is accepted to distinguish between metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO). MUHO patients have a high risk of metabolic disorders, insulin resistance, and diabetes mellitus. Among the other things, the gut microbiota also contributes to the development of metabolic disorders in obesity. Obesity is accompanied by significant changes in the gut microbial community. In turn, bacterial translocation from the intestine is the basis for the blood microbiome formation. The aim was to study the features of the blood microbiome in patients with various metabolic types of obesity. Patients, materials, methods. The study included 116 healthy donors and 101 obese patients. Depending on the metabolic type of obesity, the obese patients were divided into subgroups with MHO (n=36) and MUHO (n=53). Quantitative and qualitative assessment of the blood microbiome was based on metagenomic analysis. Blood samples were used to isolate DNA and perform sequencing of the variable v3-v4 region of the 16S rRNA gene. Alpha diversity indices (Simpson index, Shannon index, Chao1 index, phylogenetic diversity, the number of observed operational taxonomic units) were calculated. Moreover, we compared taxa (phyla, classes, orders, and families) in terms of isolation frequency and the taxon share in the total bacterial DNA pool between different patient groups. Results. In patients with MHO, the characteristics of the alpha-diversity of the blood microbiome were like those of healthy donors. However, MUHO was associated with an increase in all diversity indices. The main phyla of the blood microbiome were Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria. Cyanobacteria, TM7, Thermi, Verrucomicrobia, Chloroflexi, Acidobacteria, Planctomycetes, Gemmatimonadetes, and Tenericutes were found to be less significant phyla of the blood microbiome. Phyla Acidobacteria, TM7, and Verrucomicrobia were more often isolated in blood samples of patients with MUHO compared with healthy donors. Obese patients had a decrease in some taxonomic ranks (Bacilli, Caulobacteraceae, Barnesiellaceae, Rikenellaceae, Williamsiaceae). These changes appear to be related to the increased diversity of the blood microbiome observed in obesity. An increase of Lachnospiraceae, Succinivibrionaceae, Prevotellaceae, and S24-7 was noted for MUHO patients, which, apparently, is explained by a magnification in intestinal permeability. Conclusion. Blood microbiome differs in obese patients and healthy donors at class, order, and family levels. Moreover, the nature of the changes is determined by the metabolic type of obesity. MUHO linked to increased diversity of the blood microbiome. This appears to be due to increased microbial translocation from the intestine and non-intestinal sources.

Keywords: blood microbiome, blood bacterial DNA, obesity, metabolically healthy obesity, metabolically unhealthy obesity

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Authors: Koswaththage Dilushika Sewwandi, Aminda Lakmal

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From an activity reserved for the privileged few only some decades ago, tourism today moves more than one billion people across international borders each year. As the main part of the tourism industry, MICE tourism came to the floor and nowadays it became the main part of tourism especially in developing countries. Currently due to the fast development projects and infrastructure building, focus on tourism development in Sri Lanka could earn a global identity by practicing MICE tourism especially international conferences. Examine the behavior of conference travelers who looking for Sri Lanka as a conference destination must be required. Since the tourism industry highly involved with the personal factor and the destination selections taken by human beings it is vital to explore the factors affecting to their primary emotions which are shaped up with environmental factors. The Environmental Psychology studies the cognitive and affective behavior of human beings and based on that this study was carried out to examine the impact of environment psychology on customer primary emotions; with special reference to conference travelers to Sri Lanka. Finally, the study concludes with identifying the number of environmental factors as Accommodation, Travel Mode and Hotel Atmosphere that could impact the customer primary emotions of conference travelers to Sri Lanka.

Keywords: MICE tourism, envionmental psychology, primary emotions, destination selection

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Authors: Samia A. El-Fiky, Fouad A. Abou-Zaid, Ibrahim M. Farag, Naira M. El-Fiky

Abstract:

Clomipramine hydrochloride is one of the most used tricyclic antidepressant drug in Egypt. This drug contains in its chemical structure on two benzene rings. Benzene is considered to be toxic and clastogenic agent. So, the present study was designed to assess the genotoxic effect of Clomipramine hydrochloride on somatic and germ cells in mice. Three dose levels 0.195 (Low), 0.26 (Medium), and 0.65 (High) mg/kg.b.wt. were used. Seven groups of male mice were utilized in this work. The first group was employed as a control. In the remaining six groups, each of the above doses was orally administrated for two groups, one of them was treated for 5 days and the other group was given the same dose for 30 days. At the end of experiments, the animals were sacrificed for cytogenetic and sperm examination as well as histopathological investigations by using hematoxylin and eosin stains (H and E stains) and electron microscope. Concerning the sperm studies, these studies were confined to 5 days treatment with different dose levels. Moreover, the ultrastructural investigation by electron microscope was restricted to 30 days treatment with drug doses. The results of the dose dependent effect of Clomipramine showed that the treatment with three different doses induced increases of frequencies of chromosome aberrations in bone marrow and spermatocyte cells as compared to control. In addition, mitotic and meiotic activities of somatic and germ cells were declined. The treatments with medium or high doses were more effective for inducing significant increases of chromosome aberrations and significant decreases of cell divisions than treatment with low dose. The effect of high dose was more pronounced for causing such genetic deleterious in respect to effect of medium dose. Moreover, the results of the time dependent effect of Clomipramine observed that the treatment with different dose levels for 30 days led to significant increases of genetic aberrations than treatment for 5 days. Sperm examinations revealed that the treatment with Clomipramine at different dose levels caused significant increase of sperm shape abnormalities and significant decrease in sperm count as compared to control. The adverse effects on sperm shape and count were more obviousness by using the treatments with medium or high doses than those found in treatment with low dose. The group of mice treated with high dose had the highest rate of sperm shape abnormalities and the lowest proportion of sperm count as compared to mice received medium dose. In histopathological investigation, hematoxylin and eosin stains showed that, the using of low dose of Clomipramine for 5 or 30 days caused a little pathological changes in liver tissue. However, using medium and high doses for 5 or 30 days induced severe damages than that observed in mice treated with low dose. The treatment with high dose for 30 days gave the worst results of pathological changes in hepatic cells. Moreover, ultrastructure examination revealed, the mice treated with low dose of Clomipramine had little differences in liver histological architecture as compared to control group. These differences were confined to cytoplasmic inclusions. Whereas, prominent pathological changes in nuclei as well as dilated of rough Endoplasmic Reticulum (rER) were observed in mice treated with medium or high doses of Clomipramine drug. In conclusion, the present study adds evidence that treatments with medium or high doses of Clomipramine have genotoxic effects on somatic and germ cells of mice, as unwanted side effects. However, the using of low dose (especially for short time, 5 days) can be utilized as a therapeutic dose, where it caused relatively similar proportions of genetic, sperm, and histopathological changes as those found in normal control.

Keywords: chromosome aberrations, clomipramine, mice, histopathology, sperm abnormalities

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Authors: Aliaa Mahmoud Issa

Abstract:

Green tea may provide an alternative treatment for many skin system disorders. Intrinsic or chronological aging represents the structural, functional, and metabolic changes in the skin, which depend on the passage of time per se. The aim of the present study is to compare the effect of green tea extract administration, in drinking water or topically, on the chronological changes of the old Swiss albino mice skin. A total number of forty Swiss albino female mice (Mus musculus) were used; thirty were old females, 50-52 weeks old and the remaining ten young females were about 10 weeks old. The skin of the back of all the studied mice was dehaired with a topical depilatory cream. Treatment with green tea extract was applied in two different ways: in the drinking water (0.5mg/ml/day) or topically, applied to the skin of the dorsal side (6mg/ml water). They were divided into four main groups each of 10 animals: Group I: young untreated, Group II: old untreated groups, Group III: tea-drinking (TD) group, and Group IV: topical tea (TT) group. The animals were euthanized after 3 and 6 weeks from the beginning of green tea extract treatment. The skin was subject to morphometric (epidermal, dermal, and stratum corneum thicknesses; collagen and elastin content) studies. The skin ultrastructure of the groups treated for 6 weeks with the green tea extract was also examined. The old mouse skin was compared to the young one to investigate the chronological changes of the tissue. The results revealed that the skin of mice treated with green tea extract, either topically or to less extent in drinking water, showed a reduction in the aging features manifested by a numerical but statistically insignificant improvement in the morphometric measurements. A remarkable amelioration in the ultrastructure of the old skin was also observed. Generally, green tea extract in the drinking water revealed inconsistent results. The topical application of green tea extract to the skin revealed that the epidermal, dermal and stratum corneum thicknesses and the elastin content, that were statistically significant, approach those of the young group. The ultrastructural study revealed the same observations. The disjunction of the lower epidermal keratinocytes was reduced. It could be concluded that the topical application of green tea extract to the skin of old mice showed improvement in reversing markers of skin system aging more than using the extract in the drinking water.

Keywords: aging, green tea extract, morphometry, skin, ultrastructure

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Authors: Bui Phuong Linh, Yuki Sakakibara, Ryuto Tanaka, Elizabeth H. Pigney, Taishi Hashiguchi

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Non-alcoholic steatohepatitis (NASH) is a chronic liver disease, often associated with type II diabetes, which sometimes progresses to more serious conditions such as liver fibrosis and hepatocellular carcinoma (HCC). NASH has become an important health problem worldwide, buttherapeutic agents for NASH have not yet been approved, and animal models with high clinical correlation are required. TheSTAM™ mouse shows the same pathological progression as human NASH patients and has been widely used for both drug efficacy and basic research, such as lipid profiling and gut microbiota research. In this study, we analyzed the RNA-seq data of STAM™mice at each pathological stage (steatosis, steatohepatitis, liver fibrosis, and HCC) and examined the clinical correlation at the genetic level. NASH was induced in male mice by a single subcutaneous injection of 200 µg streptozotocin solution 2 days after birth and feeding with high fat dietafter 4 weeks of age. The mice were sacrificed and livers collected at 6, 8, 10, 12, 16, and 20 weeks of age. For liver samples, the left lateral lobe was snap frozen in liquid nitrogen and stored at -80˚C for RNA-seq analysis. Total RNA of the cells was isolated using RNeasy mini kit. The gene expression of the canonical pathways in NASH progression from steatosis to hepatocellular carcinoma were analyzed, such as immune system process, oxidation-reduction process, lipid metabolic process. Moreover, since it has been reported that genetic traits are involved in the development of NASH-HCC, we next analyzed the genetic mutations in the STAM™mice. The number of individuals showing mutations in Mtorinvolved in Insulin signaling increases as the disease progresses, especially in the liver cancer phase. These results indicated a clinical correlation of gene profiles in the STAM™mouse.

Keywords: steatosis, non-alcoholic steatohepatitis, fibrosis, hepatocellular carcinoma, RNA-seq

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Authors: Göksel Doğan, Murat Öztürk, Didar Tuğçe Karakulak, Mehmet Nurullah Orman, Nicolas Sylvius, Matthew Blades, Mustafa Sandıkçı, Cengiz Ünsal, Mehtap Kılıç Eren, Funda Kıral, Levent Karagenç

Abstract:

Assisted reproduction is associated with impaired glucose metabolism in adulthood. miRNAs are key regulators of glucose metabolism. Whether embryo culture and/or transfer alters the expression of miRNAs and to what extent this process affects glucose metabolism remain largely unknown. The purpose of the present study was to examine the expression of miRNAs in the liver in mice obtained by the transfer of blastocysts. The study was comprised of an experimental (EG) and a control group (CG). EG was generated by embryo transfer to pseudo-pregnant females. Mice born from naturally ovulating females were used as the CG. Differential expression of miRNAs, blood glucose, plasma insulin, liver glycogen, and activities of some of the rate-limiting enzymes involved in glucose metabolism were determined at ten weeks of age. Blood glucose, plasma insulin, and glycogen concentrations were similar between the groups in both sexes. Activities of enzymes were similar among females. EG males had significantly less glucokinase and phosphofructokinase activity compared to CG males. None of the miRNAs were differentially expressed in males. On the other hand, miR-143-3p expression was upregulated in EG females. Expression of none of the genes targeted by miR143-3p differed between the groups. These results demonstrate that miR143-3p, a novel regulator of type 2 diabetes, is upregulated in mice generated by assisted reproduction in a sexually-dimorphic manner with no apparent effect on glucose and insulin levels at ten weeks of age. It remains to be determined if this process is associated with impaired glucose homeostasis in the long term.

Keywords: assisted reproduction, blastocyst, embryo culture, glucose metabolism, miR143-3p, oxygen

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Authors: Brahmanage S. Rangika, Dinithi C. Peiris

Abstract:

Boiled Aqueous Flower Extract (AFE) of Nyctanthes arbor-tristis L. (Family: Oleaceae) is used in traditional Sri Lankan medicinal system to treat diabetes. However, this is not scientifically proven and the mechanisms by which the flowers reduce diabetes have not been investigated. The present study was carried out to examine the hypoglycemic potential and toxicity effects of aqueous flower extract of N. arbor-tristis. AFE was prepared and mice were treated orally either with 250, 500, and 750 mg/kg of AFE or distilled water (Control). Fasting and random blood glucose levels were determined. In addition, the toxicity of AFE was determined using chronic oral administration. In normoglycemic mice, mid dose (500mg/kg) of AFE significantly (p < 0.01) reduced fasting blood glucose levels by 49% at 4h post treatment. Further, 500mg/kg of AFE significantly (p < 0.01) lowered random blood glucose level of non-fasted normoglycemic mice. AFE significantly lowered total cholesterol and triglyceride levels while increasing the HDL levels in the serum. Further, AFE significantly inhibited the glucose absorption from the lumen of the intestine and it increases the diaphragm uptake of glucose. Alpha-amylase inhibitory activity was also evident. However, AFE did not induce any overt signs of toxicity or hepatotoxicity. There were no adverse effects on food and water intake and body weight of mice during the experimental period. It can be concluded that AFE of N. arbor-tristis posses safe oral anti diabetic potentials mediated via multiple mechanisms. Results of the present study scientifically proved the claims made about the uses of N. arbor-tristis in the treatment of diabetes mellitus in traditional Sri Lankan medicinal system. Further, flowers can also be used for as a remedy to improve blood lipid profile.

Keywords: aqueous extract, hypoglycemic hypolipidemic, Nyctanthes arbor-tristis flowers, hepatotoxicity

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Authors: Khayra Zerrouki, Noureddine Djebli, Esra Eroglu, Afife Mat, Ozhan Gul

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Neurodegenerative diseases of the human brain comprise a variety of disorders that affect an increasing percentage of the population. Alzheimer’s disease (AD) is a complex, multifactorial, heterogeneous mental illness, which is characterized by an age-dependent loss of memory and an impairment of multiple cognitive functions, but this 10 last years it concerns the population most and most young. Hypericum perforatum has traditionally been used as an external anti-inflammatory and healing remedy for the treatment of swellings, wounds and burns, diseases of the alimentary tract and psychological disorders. It is currently of great interest due to new and important therapeutic applications. In this study, the chemical composition of methanolic extract of Hypericum perforatum (HPM) was analysed by using high performance liquid chromatography – diode array detector (HPLC-DAD). The in vitro antioxidant activity of HPM was evaluated by using several antioxidant tests. HSM exhibits inhibitory capacity against posphatidylcholine liposome peroxidation, induced with iron and ascorbic acid, scavenge DPPH and superoxide radicals and act as reductants. The cytotoxic activity of HSM was also determined by using MTT cell viability assay on HeLa and NRK-52E cell lines. The in vivo activity studies in Swiss mice were determined by using behavioral, memory tests and histological study. According to tests results HPM that may be relevant to the treatment of cognitive disorders. The results of chemical analysis showed a hight level of hyperforin and quercitin that had an important antioxidant activity proved in vitro with the DPPH, anti LPO and SOD; this antioxidant activity was confirmed in vivo after the non-toxic results by means of improvement in behavioral and memory than the reducing shrunken in pyramidal cells of mice brains.

Keywords: AlCl3, alzheimer, mice, neuroprotective, neurotoxicity, phytotherapy

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Authors: Yu-Ling Tsai, Chih-Jung Chang, Chia-Chen Lu, Eric Wu, Chuan-Sheng Lin, Tzu-Lung Lin, Hsin-Chih Lai

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It is urgent that novel anti-obesity measures that are safe, effective and widely available are developed for counteracting the rapidly growing obesity epidemics. In the present study, we show that a probiotic bacterium Parabacteroides goldsteinii screened through culture under the high molecular weight polysaccharides prepared from two iconic medicinal fungi, the Ganoderma lucidum and the Hirsutella sinensis, reduced body weight by ca. 20% in high-fat diet (HFD)-fed mice. The bacterium also decreased intestinal permeability, metabolic endotoxemia, inflammation and insulin resistance. Notably, oral administration of live, but not high temperature-killed, P. goldsteinii to HFD fed mice considerably reduces weight gain and obesity-associated metabolic disorders. A three months feeding of the mice with P. goldsteinii did not show any aberrant side effects, indicating the safety of this bacterium. Transcriptome analysis indicated that P. goldsteinii enhances immunity in resting dendritic cells, but reduces inflammation in lipopolysaccharide (LPS)-induced dendritic cells. On top, Naïve T-cells were skewed towards regulatory T-cells after encountering with dendritic cells (DCs) pretreated with P. goldsteinii. These results indicated P. goldsteinii showed anti-inflammatory effects and can work as a potential probiotic ameliorating obesogenicity and related metabolic syndromes.

Keywords: Parabacteroides goldsteinii, gut microbiome, obesity, immune modulation

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Authors: Diea Gamal Abo El-Hassan, Salwa Ahmed Aly, Abdelrahman Mahmoud Abdelgwad

Abstract:

The major conjugated linoleic acid (CLA) isomers have anticancer effect, especially breast cancer cells, inhibits cell growth and induces cell death. Also, CLA has several health benefits in vivo, including antiatherogenesis, antiobesity, and modulation of immune function. The present study aimed to assess the safety and anticancer effects of milk fat CLA against in vivo Ehrlich ascites carcinoma (EAC) in female Swiss albino mice. This was based on acute toxicity study, detection of the tumor growth, life span of EAC bearing hosts, and simultaneous alterations in the hematological, biochemical, and histopathological profiles. Materials and Methods: One hundred and fifty adult female mice were equally divided into five groups. Groups (1-2) were normal controls, and Groups (3-5) were tumor transplanted mice (TTM) inoculated intraperitoneally with EAC cells (2×106 /0.2 mL). Group (3) was (TTM positive control). Group (4) TTM fed orally on balanced diet supplemented with milk fat CLA (40 mg CLA/kg body weight). Group (5) TTM fed orally on balanced diet supplemented with the same level of CLA 28 days before tumor cells inoculation. Blood samples and specimens from liver and kidney were collected from each group. The effect of milk fat CLA on the growth of tumor, life span of TTM, and simultaneous alterations in the hematological, biochemical, and histopathological profiles were examined. Results: For CLA treated TTM, significant decrease in tumor weight, ascetic volume, viable Ehrlich cells accompanied with increase in life span were observed. Hematological and biochemical profiles reverted to more or less normal levels and histopathology showed minimal effects. Conclusion: The present study proved the safety and anticancer efficiency of milk fat CLA and provides a scientific basis for its medicinal use as anticancer attributable to the additive or synergistic effects of its isomers.

Keywords: anticancer activity, conjugated linoleic acid, Ehrlich ascites carcinoma, % increase in life span, mean survival time, tumor transplanted mice.

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Authors: Adela Penesova, Zofia Radikova, Boris Bajer, Andrea Havranova, Miroslav Vlcek

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Background: The aim of our study was to compare the effect of intensified lifestyle intervention on insulin resistance (HOMA-IR), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and Fibroblast growth factor (FGF) 21 after 8 weeks of lifestyle intervention. Methods: A group of 43 obese patients (13M/30F; 43.0±12.4 years; BMI (body mass index) 31.2±6.3 kg/m2 participated in a weight loss interventional program (NCT02325804) following an 8-week hypocaloric diet (-30% energy expenditure) and physical activity 150 minutes/week. Insulin sensitivity was evaluated according to the homeostasis model assessment of insulin resistance (HOMA-IR) and insulin sensitivity indices according to Matsuda and Cederholm were calculated (ISImat and ISIced). Plasma ALT, AST, Fetuin-A, FGF 21, and physical fitness were measured. Results: The average reduction of body weight was 6.8±4.9 kg (0-15 kg; p=0.0006), accompanied with a significant reduction of body fat amount of fat mass (p=0.03), and waist circumference (p=0.02). Insulin sensitivity has been improved (IR HOMA 2.71±3.90 vs 1.24±0.83; p=0.01; ISIMat 6.64±4.38 vs 8.93±5.36 p ≤ 0.001). Total, LDL cholesterol, and triglycerides decreased (p=0.05, p=0.04, p=0.04, respectively). Physical fitness significantly improved after intervention (as measure VO2 max (maximal oxygen uptake) (p ≤ 0.001). ALT decreased significantly (0.44±0.26 vs post 0.33±0.18 ukat/l, p=0.004); however, AST not (pre 0.40±0.15 vs 0.35±0.09 ukat/l, p=0.07). Hepatokine Fetuin-A significantly decreased after intervention (43.1±10.8 vs 32.6±8.6 ng/ml, p < 0.001); however, FGF 21 levels tended to decrease (146±152 vs 132±164 pg/ml, p=0.07). Conclusion: 8-weeks of diet and physical activity intervention program in obese otherwise healthy subjects led to an improvement of insulin resistance parameters and liver marker profiles, as well as increased physical fitness. This study was supported by grants APVV 15-0228; VEGA 2/0161/16.

Keywords: obesity, diet, exercice, insulin sensitivity

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Authors: Seongho Jang

Abstract:

Objective: To investigate an appropriate depth of needle insertion during trigger point injection into the rhomboid major muscle. Methods: Sixty-two patients who visited our department with shoulder or upper back pain participated in this study. The distance between the skin and the rhomboid major muscle (SM) and the distance between the skin and rib (SB) were measured using ultrasonography. The subjects were divided into 3 groups according to BMI: BMI less than 23 kg/m2 (underweight or normal group); 23 kg/m2 or more to less than 25 kg/m2 (overweight group); and 25 kg/m2 or more (obese group). The mean ±standard deviation (SD) of SM and SB of each group were calculated. A range between mean+1 SD of SM and the mean-1 SD of SB was defined as a safe margin. Results: The underweight or normal group’s SM, SB, and the safe margin were 1.2±0.2, 2.1±0.4, and 1.4 to 1.7 cm, respectively. The overweight group’s SM and SB were 1.4±0.2 and 2.4±0.9 cm, respectively. The safe margin could not be calculated for this group. The obese group’s SM, SB, and the safe margin were 1.8±0.3, 2.7±0.5, and 2.1 to 2.2 cm, respectively. Conclusion: This study will help us to set the standard depth of safe needle insertion into the rhomboid major muscle in an effective manner without causing any complications.

Keywords: pneumothorax, rhomboid major muscle, trigger point injection, ultrasound

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Authors: Narin Ozturk, Xiao-Mei Li, Sylvie Giachetti, Francis Levi, Alper Okyar

Abstract:

P-glycoprotein (P-gp, MDR1, ABCB1) is a transmembrane protein acting as an ATP-dependent efflux pump and functions as a biological barrier by extruding drugs and xenobiotics out of cells in healthy tissues especially in intestines, liver and brain as well as in tumor cells. The circadian timing system controls a variety of biological functions in mammals including xenobiotic metabolism and detoxification, proliferation and cell cycle events, and may affect pharmacokinetics, toxicity and efficacy of drugs. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer drug that is active against many cancers, and its pharmacokinetics depend on P-gp. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus with respect to the intestinal P-gp expression rhythms in mdr1a::Luc mice using Real Time-Biolumicorder (RT-BIO) System. Mdr1a::Luc male mice were synchronized with 12 h of Light and 12 h of Dark (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding Light onset). After 1-week baseline recordings, everolimus (5 mg/kg/day x 14 days) was administered orally at ZT1-resting period- and ZT13-activity period- to mdr1a::Luc mice singly housed in an innovative monitoring device, Real Time-Biolumicorder units which let us monitor real-time and long-term gene expression in freely moving mice. D-luciferin (1.5 mg/mL) was dissolved in drinking water. Mouse intestinal mdr1a::Luc oscillation profile reflecting P-gp gene expression and locomotor activity pattern were recorded every minute with the photomultiplier tube and infrared sensor respectively. General behavior and clinical signs were monitored, and body weight was measured every day as an index of toxicity. Drug-induced body weight change was expressed relative to body weight on the initial treatment day. Statistical significance of differences between groups was validated with ANOVA. Circadian rhythms were validated with Cosinor Analysis. Everolimus toxicity changed as a function of drug timing, which was least following dosing at ZT13, near the onset of the activity span in male mice. Mean body weight loss was nearly twice as large in mice treated with 5 mg/kg everolimus at ZT1 as compared to ZT13 (8.9% vs. 5.4%; ANOVA, p < 0.001). Based on the body weight loss and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13. Both rest-activity and mdr1a::Luc expression displayed stable 24-h periodic rhythms before everolimus and in both vehicle-treated controls. Real-time bioluminescence pattern of mdr1a revealed a circadian rhythm with a 24-h period with an acrophase at ZT16 (Cosinor, p < 0.001). Mdr1a expression remained rhythmic in everolimus-treated mice, whereas down-regulation was observed in P-gp expression in 2 of 4 mice. The study identified the circadian pattern of intestinal P-gp expression with an unprecedented precision. The circadian timing depending on the P-gp expression rhythms may play a crucial role in the tolerability/toxicity of everolimus. The circadian changes in mdr1a genes deserve further studies regarding their relevance for in vitro and in vivo chronotolerance of mdr1a-transported anticancer drugs. Chronotherapy with P-gp-effluxed anticancer drugs could then be applied according to their rhythmic patterns in host and tumor to jointly maximize treatment efficacy and minimize toxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, mdr1a::Luc mice, p-glycoprotein

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Authors: Kiran Shehzadi, Yasmeen Akhtar, Mujahid Ameen, Tabinda Ijaz, Shoukat Siddique

Abstract:

Nanoparticles, due to their different sizes and morphologies, are employed in various fields such as the medical field, cosmetics, pharmaceutical, textile industry as well as in paints, adhesives, and electronics. Metal nanoparticles exhibit excellent antimicrobial activity, dye degradation and can be used as anti-cancerous drug loading agents. In this study, sZilver nanoparticles (Ag-NPs) were synthesized employing doxycycline (antibiotic) as a reducing and capping agent (biological/green synthesis). Produced Ag-NPS were characterized using UV/VIS spectrophotometry, XRD, SEM, and FTIR. Surface plasmon resonance (SPR) of silver nanoparticles was observed at 411nm with 90nm size with homogenized spherical shape. These particles revealed good inhibition zones for Fungi such as Candida albicans and Candida tropicalis. In this study, toxic properties of Ag-NPs were monitored by allowing them to penetrate in the cell, causing an abrupt increase in oxidative stress, which resulted ultimately in cell death. Histopathological analysis of mice organs was performed by administering definite concentrations of silver nanoparticles orally to mice for 14 days. Toxic properties were determined, and it was revealed that the toxicity of silver nanoparticles mainly depends on the size. Silver nanoparticles of this work presented mild toxicity for different organs (liver, kidney, spleen, heart, and stomach) of mice.

Keywords: metal nanoparticles, green/biological methods, toxicity, Candida albicans, Candida tropicalis

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Authors: Sweta Pandey, Samridhi Dhyani, Susmita Chaudhuri

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Klebsiella pneumoniae bacteria is a global threat to human health due to an increase in multi-drug resistance among strains. The hypervirulent strains of Klebsiella pneumoniae is a major trouble due to their association with life-threatening infections in a healthy population. One of the major virulence factors of hyper virulent strains of Klebsiella pneumoniae is the T6SS (Type six secretary system) which is majorly involved in microbial antagonism and causes interaction with the host eukaryotic cells during infections. T6SS mediates some of the crucial factors for establishing infection by the bacteria, such as cell adherence, invasion, and subsequent in vivo colonisation. The antibacterial activity and the cell invasion property of the T6SS system is a major requirement for the establishment of K. pneumoniae infections within the gut. The T6SS can be an appropriate target for developing therapeutics. The T6SS consists of an inner tube comprising hexamers of Hcp (Haemolysin -regulated protein) protein, and at the top of this tube sits VgrG (Valine glycine repeat protein G); the tip of the machinery consists of PAAR domain containing proteins which act as a delivery system for bacterial effectors. For this study, immune response to recombinant VgrG protein was generated to establish this protein as a potential immunogen for the development of therapeutic leads. The immunogenicity of the selected protein was determined by predicting the B cell epitopes by the BCEP analysis tool. The gene sequence for multiple domains of VgrG protein (phage_base_V, T6SS_Vgr, DUF2345) was selected and cloned in pMAL vector in E. coli. The construct was subcloned and expressed as a fusion protein of 203 residue protein with mannose binding protein tag (MBP) to enhance solubility and purification of this protein. The purified recombinant VgrG fusion protein was used for mice immunisation. The antiserum showed reactivity with the recombinant VgrG in ELISA and western blot. The immunised mice were challenged with K. pneumoniae bacteria and showed bacterial clearance in immunised mice. The recombinant VgrG protein can further be used for studying downstream signalling of VgrG protein in mice during infection and for therapeutic MAb development to eradicate K. pneumoniae infections.

Keywords: immune response, Klebsiella pneumoniae, multi-drug resistance, recombinant protein expression, T6SS, VgrG

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