Search results for: idiopathic inflammatory myopathies

Authors: Kamsiah Jaarin, Yusof Kamisah, Faizah Othman Nurul Akmal Muhammad, Zakiah Jubri, Qodriyah Mohd Saad, Srijit Das

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Forty (40) normotensive adult male Sprague-Dawley rats aged three months weighing 180-200 g were divided into 4 groups with 10 rats per group: (1) normotensive control; (2) hypertensive rats; (3) hypertensive rats treated with Nigella sativa (2.5 ml/kg/day); and (4) hypertensive rats treated with nicardipine (5 mg/kg/day). After acclimatization, the hypertensive rats of the group 2, 3 and 4 were induced to be hypertensive by giving NW–nitro-L-arginine methyl ester (L-NAME; 30 mg/kg/day) in their drinking water for consecutive 7 days. After one week, rats in the group 3 were given a daily oral dose of 2.5 ml/kg/day of Nigella sativa (NS) by oral gavage. Rats in the group 4 were given nicardipine (5 mg/kg/day) via oral gavages. All rats in this study received L-NAME continuously throughout the treatment duration. The blood pressure will be measured pre-treatment and weekly for 8 weeks using power lab. Blood was taken before and at the end of study for measurement of nitric oxide. At the end of 8 weeks, the rats are sacrificed and descending thoracic aorta was disserted for measurement of vascular reactivity, and intracellular adhesion molecules (ICAM-1) and vascular cell adhesion molecules (VCAM-1). Nigella sativa reduced both systolic and diastolic BP compared to control and L-name group. The BP lowering effect of NS was comparable to nicardipine a calcium antagonist. The blood pressure lowering effect of NS was accompanied with an increasing relaxation response to nitroprusside and acetylcholine and reducing vasoconstriction response to epinephrine. L-NAME and nicardipine on the other hand, reduced plasma nitric oxide concentration. In contrast, NS increased NO concentration. However, Nigella sativa had no significant effect on aortic VCAM- 1 and ICAM-1 expression. In conclusion; Nigella sativa oil reduces both systolic and diastolic blood pressure in L-NAME treated rats. The antihypertensive effect of NS was comparable to nicardipine. The BP lowering effect may be mediated via stimulating nitric oxide release from vascular endothelium.

Keywords: Nigella sativa, ICAM, VCAM, blood pressure, vascular reactivity

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Authors: Shilu Deepa Thomas, P. Jayaprakash, Dorota Łazewska, Katarzyna Kieć-Kononowicz, B. Sadek

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A large body of evidence suggests the involvement of cognitive impairment, increased levels of inflammation and oxidative stress in the pathogenesis of autism spectrum disorder (ASD). ASD commonly coexists with psychiatric conditions like anxiety and cognitive challenges, and individuals with ASD exhibit significant levels of inflammation and immune system dysregulation. Previous Studies have identified elevated levels of pro-inflammatory markers such as IL-1β, IL-6, IL-2 and TNF-α, particularly in young children with ASD. The current therapeutic options for ASD show limited effectiveness, signifying the importance of exploring an efficient drugs to address the core symptoms. The role of histamine H3 receptors (H3Rs) in memory and the prospective role of H3R antagonists in pharmacological control of neurodegenerative disorders, e.g., ASD, is well-accepted. Hence, the effects of chronic systemic administration of H3R antagonist E159 on autistic-like repetitive behaviors, social deficits, memory and anxiety parameters, as well as neuroinflammation in Black and Tan BRachyury (BTBR) mice, were evaluated using Y maze, Barnes maze, self-grooming, open field and three chamber social test. E159 (2.5, 5 and 10 mg/kg, i.p.) dose-dependently ameliorated repetitive and compulsive behaviors by reducing the increased time spent in self-grooming and improved reduced spontaneous alternation in BTBR mice. Moreover, treatment with E159 attenuated disturbed anxiety levels and social deficits in tested male BTBR mice. Furthermore, E159 attenuated oxidative stress by significantly increasing GSH, CAT, and SOD and decreasing the increased levels of MDA in the cerebellum as well as the hippocampus. In addition, E159 decreased the elevated levels of proinflammatory cytokines (tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and IL-6). The observed results show that H3R antagonists like E159 may represent a promising novel pharmacological strategy for the future treatment of ASD.

Keywords: histamine H3 receptors, antagonist E159, autism, behaviors, mice

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Authors: Qunying Yuan, Manjula Bomma, Adrian Rhoden, Zhigang Xiao

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Selenium is an essential micronutrient for all mammals and plays an important role in maintaining human physiological functions. The potential applications of selenium as food supplements, cancer-prevention, antimicrobial and anti-inflammatory agents have been investigated in biomedicine and food sciences. Nanoscale of selenium is of particular interest due to its better biocompatibility, higher bioavailability, lower toxicity, more homogeneous distribution, and presumptive controlled release of substances. The objective of this study is to explore whether selenium nanoparticle (SeNP) has the potential to be used as a food preservative to reduce food spoilage. SeNPs were synthesized through ascorbic acid reduction of sodium selenite using the bovine serum albumin (BSA) as capping and stabilizing agent. The chemically synthesized SeNPs had a spherical conformation and a size of 22.8 ± 4.7 nm. FTIR analysis confirmed that the nanoparticles were covered with BSA. We further tested the antimicrobial activity of these SeNPs against common food-borne bacteria. Colony forming unit assay showed that SeNPs exhibited good inhibition on the growth of Listeria Monocytogens (ATCC15313), Staphylococcus epidermidis (ATCC 700583) starting at 0.5µg/mL, but only a moderate inhibitory effect on the growth of Staphylococcus aureus (ATCC12600) and Vibrio alginolyticus (ATCC 33787) at a concentration higher than 10µg/mL and 2.5µg/mL, respectively. There was a mild effect against the growth Salmonella enterica (ATCC19585) when the concentration reached 15µg/mL. No inhibition was observed in the growth of Enterococcus faecalis (ATCC 19433). Surprisingly, SeNPs appeared to promote the growth of Vibrio parahaemolyticus (ATCC43996) and Salmonella enterica (ATCC49284) at 30 µg/mL and above. Our preliminary data suggested that the chemically synthesized SeNPs may be able to inhibit some food-borne bacteria, and SeNP as a food preservative should be used with caution. We will explore the mechanisms of the inhibitory action of chemically synthesized SeNPs on bacterial growth and whether the SeNPs are able to inhibit the development of biofilm and antibiotic resistance.

Keywords: antimicrobial, food-borne bacteria, nanoparticles, selenium

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Authors: Lohendy Munoz-Vargas, Stephen O. Opiyo, Rose Digianantonio, Michele L. Williams, Asela Wijeratne, Gregory Habing

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Non-typhoidal Salmonella enterica is a zoonotic pathogen with critical importance in animal and public health. The persistence of Salmonella on farms affects animal productivity and health, and represents a risk for food safety. The intestinal microbiota plays a fundamental role in the colonization and invasion of this ubiquitous microorganism. To overcome the colonization resistance imparted by the gut microbiome, Salmonella uses invasion strategies and the host inflammatory response to survive, proliferate, and establish infections with diverse clinical manifestations. Cattle serve as reservoirs of Salmonella, and periparturient cows have high prevalence of Salmonella shedding; however, to author`s best knowledge, little is known about the association between the gut microbiome and the onset of Salmonella shedding during the periparturient period. Thus, the objective of this study was to assess the association between changes in bacterial communities and the onset of Salmonella shedding in cattle approaching parturition. In a prospective cohort study, fecal samples from 98 dairy cows originating from four different farms were collected at four time points relative to calving (-3 wks, -1 wk, +1 wk, +3 wks). All 392 samples were cultured for Salmonella. Sequencing of the V4 region of the 16S rRNA gene using the Illumina platform was completed to evaluate the fecal microbiome in a selected sample subset. Analyses of microbial composition, diversity, and structure were performed according to time points, farm, and Salmonella onset status. Individual cow fecal microbiomes, predominated by Bacteroidetes, Firmicutes, Spirochaetes, and Proteobacteria phyla, significantly changed before and after parturition. Microbial communities from different farms were distinguishable based on multivariate analysis. Although there were significant differences in some bacterial taxa between Salmonella positive and negative samples, our results did not identify differences in the fecal microbial diversity or structure for cows with and without the onset of Salmonella shedding. These data suggest that determinants other than the significant changes in the fecal microbiome influence the periparturient onset of Salmonella shedding in dairy cattle.

Keywords: dairy cattle, microbiome, periparturient, Salmonella

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Authors: Yifat Koren Carmi, Abed Agbarya, Hazem Khamaisi, Raymond Farah, Yelena Shechtman, Roman Korobochka, Jacob Gopas, Jamal Mahajna

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Ovarian cancer (OC), the second most common form of gynecological malignancy, has a poor prognosis and is frequently identified in its late stages. The recommended treatment for OC typically includes a platinum-based chemotherapy, like carboplatin. Nonetheless, OC treatment has proven challenging due to toxicity and development of acquired resistance to therapy. Chemoresistance is a significant obstacle to a long-lasting response in OC patients, believed to arise from alterations within the cancer cells as well as within the tumor microenvironments (TME). Malignant ascites is a presenting feature in more than one-third of OC patients. It serves as a reservoir for a complex mixture of soluble factors, metabolites, and cellular components, providing a pro-inflammatory and tumor-promoting microenvironment for the OC cells. Malignant ascites is also associated with metastasis and chemoresistance. In an attempt to elucidate the role of TME in chemoresistance of OC, we monitored the ability of soluble factors derived from ascites fluids to affect platinum sensitivity of OC cells. This research, compared ascites fluids from non-malignant cirrhotic patients to those from OC patients in terms of their ability to alter the platinum sensitivity of OC cells. Our findings indicated that exposure to OC ascites induces platinum chemoresistance on OC cells in 11 out of 13 cases (85%). In contrast, 75% of cirrhosis ascites (3 out of 4) failed to confer platinum chemoresistance to OC cells. Cytokine array analysis revealed that IL-6, and to a lesser extent HGF were enriched in OC ascites, whereas IL-22 was enriched in cirrhosis ascites. Pharmaceutical inhibitors that target the IL-6/JAK signaling pathway were mildly effective in overcoming the platinum chemoresistance induced by malignant ascites. In contrast, Crizotinib an HGF/c-MET inhibitor, and 2-hydroxyestradiol (2HE2) were effective in restoring platinum chemoresistance to OC. Our findings demonstrate the importance of OC ascites in supporting platinum chemoresistance as well as the potential of a combination therapy with Crizotinib and the estradiol metabolite 2HE2 to regain OC cells chemosensitivity.

Keywords: ovarian cancer, platinum chemoresistance, malignant ascites, tumor microenvironment, IL-6, 2-hydroxyestradiol, HGF, crizotinib

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Authors: G. Lambe, D. Mansukhani, A. Shetty, S. Khodaiji, C. Rodrigues, F. Kapadia

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Introduction: Sepsis is known to cause impairment of both innate and adaptive immunity and involves an early uncontrolled inflammatory response, followed by a protracting immunosuppression phase, which includes decreased expression of cell receptors, T cell anergy and exhaustion, impaired cytokine production, which may cause high risk for secondary infections due to reduced response to antigens. Although human cytomegalovirus (CMV) is widely recognized as a serious viral pathogen in sepsis and immunocompromised patients, the incidence of CMV reactivation in patients with sepsis lacking strong evidence of immunosuppression is not well defined. Therefore, it is important to determine an association between CMV reactivation and sepsis-induced immunosuppression. Aim: To determine the association between incidence of CMV reactivation and immune modulation in sepsis-induced immunosuppression with time. Material and Methods: Ten CMV-seropositive adult patients with severe sepsis were included in this study. Blood samples were collected on Day 0, and further weekly up to 21 days. CMV load was quantified by real-time PCR using plasma. The expression of immunosuppression markers, namely, HLA-DR, PD-1, and regulatory T cells, were determined by flow cytometry using whole blood. Results: At Day 0, no CMV reactivation was observed in 6/10 patients. In these patients, the median length for reactivation was 14 days (range, 7-14 days). The remaining four patients, at Day 0, had a mean viral load of 1802+2599 copies/ml, which increased with time. At Day 21, the mean viral load for all 10 patients was 60949+179700 copies/ml, indicating that viremia increased with the length of stay in the hospital. HLA-DR expression on monocytes significantly increased from Day 0 to Day 7 (p = 0.001), following which no significant change was observed until Day 21, for all patients except 3. In these three patients, HLA-DR expression on monocytes showed a decrease at elevated viral load (>5000 copies/ml), indicating immune suppression. However, the other markers, PD-1 and regulatory T cells, did not show any significant changes. Conclusion: These preliminary findings suggest that CMV reactivation can occur in patients with severe sepsis. In fact, the viral load continued to increase with the length of stay in the hospital. Immune suppression, indicated by decreased expression of HLA-DR alone, was observed in three patients with elevated viral load.

Keywords: CMV reactivation, immune suppression, sepsis immune modulation, CMV viral load

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Authors: Xiaoquan Huang, Congcong Li, Tingting Wei, Changcun Bai, Na Liu, Meng Tang

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Silver is often doped on nano-titanium dioxide photocatalysts (Ag-TiO₂) by photodeposition method to improve their utilization of visible-light while increasing the toxicity of TiO₂。 However, it is not known what factors influence this toxicity and how to reduce toxicity while maintaining the maximum catalytic activity. In this study, Ag-TiO₂ photocatalysts were synthesized by the photodeposition method with different silver content (AgC) and photodeposition time (PDT). Characterization and catalytic experiments demonstrated that silver was well assembled on TiO₂ with excellent visible-light catalytic activity, and the size of silver increased with PDT. In vitro, the cell viability of lung epithelial cells A549 and BEAS-2B showed that the higher content and smaller size of silver doping caused higher toxicity. In vivo, Ag-TiO₂ catalysts with lower AgC or larger silver particle size obviously caused less pulmonary pro-inflammatory and pro-fibrosis responses. However, the visible light catalytic activity decreased with the increase in silver size. Therefore, in order to optimize the Ag-TiO₂ photocatalyst with the lowest pulmonary toxicity and highest catalytic performance, response surface methodology (RSM) was further performed to optimize the two independent variables of AgC and PDT. Visible-light catalytic activity was evaluated by the degradation rate of Rhodamine B, the antibacterial property was evaluated by killing log value for Escherichia coli, and cytotoxicity was evaluated by IC50 to BEAS-2B cells. As a result, the RSM model showed that AgC and PDT exhibited an interaction effect on catalytic activity in the quadratic model. AgC was positively correlated with antibacterial activity. Cytotoxicity was proportional to AgC while inversely proportional to PDT. Finally, the optimization values were AgC 3.08 w/w% and PDT 28 min. Under this optimal condition, the relatively high silver proportion ensured the visible-light catalytic and antibacterial activity, while the longer PDT effectively reduced the cytotoxicity. This study is of significance for the safe and efficient application of silver-doped TiO₂ photocatalysts.

Keywords: Ag-doped TiO₂, cytotoxicity, inflammtion, fibrosis, response surface methodology

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Authors: Ilirian Laçi, Alketa Spahiu

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Big strums of thyroid glandule observed by a simple viewing can be witnessed in everyday life. Medical cabinets evidence patients withpalpablenodes of thyroid glandule, mainly nodes of the size of 10 millimeters. Further, more cases which have resulted in negative under palpation have resulted in positive at ultrasound examination. Therefore, the use of ultrasound for diagnosing has increased the number of patients with nodes of thyroid glandule in the last couple of decades in all countries, Albania included. Thus, there has been evidence of an increased number of patients affected by this pathology, where female patients dominate. Demographically, the capital shows high numbers due to the high population, but of interest is the high incidence of those areas distanced from the sea. While regarding related pathologies, no significant link was evidenced, an element of ancestry was evident in the nodes of the thyroid glandule. When we talk of nodes of the thyroid glandule, we should consider hyperplasia, neoplasia, and inflammatory diseases that cause nodes of the thyroid glandule. This increase parallels the world’s increase of the incidence of thyroid glandule, with malign cases, which are at about 5% and are not depended on size. Given the numbers, with most thyroid glandule nodes being benign, the main objective of the examination of the nodes was the determination of benign and malign cases to avoid undue surgery. Subject of this study were 212 patients that underwent fine-needle aspiration (FNA) under ultrasound guidance at the Medical University Center of Tirana. All the patients came to the Mother Teresa University Hospital from public and private hospitals and other polyclinics. These patients had an ultrasound examination before visiting the Center of Nuclear Medicine for a scintigraph of thyroid glandule in the period September 2016 and September 2017. To correlate, all patients had been examined via ultrasound of the thyroid glandule prior to the scintigraph. The ultrasound included evaluation of the number of nodes, their size, their solid, cystic, or solid-cystic structure, echogenicity according to the gray scale, the presence of calcification, the presence of lymph nodes, the presence of adenopathy, and the correlation of the cytology results from the Laboratory of Pathological Anatomy of Medical University Center of Tirana.

Keywords: thyroid nodes, fine needle aspiration, ultrasound, scintigraphy

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Authors: John Olayinka Atoyebi

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Developing countries like Nigeria are facing myriad problems, ranging from economic challenges, lack of no jobs, food insecurity, malnutrition, and poverty. However, tackling some of these menaces is not just a trivial issue neither do some of them require rocket science to fix, but rather the understanding of every individual citizen recognizing their respective roles that they have to play in making the country better, rather than putting all the blames on the Government. Tackling nutrition and food insecurity is a complex problem, but this work examines what an individual can do to improve nutrient consumption. Leafy indigenous vegetables can be termed as functional foods since they are very rich in nutrients, phytochemicals and other beneficial compounds to the body system. These functional foods are the class that provides necessary health benefits beyond basic nutrition. Usually functional foods often contain bioactive compounds, which help the body through the prevention and management of various diseases, as well as improving the overall health of human beings. The analysis carried out on some Nigerian leafy indigenous vegetables in home grown setting revealed, for example, the potential use of Iron (Fe) amount of 318.15ppm in Basella alba (red species) and that of Telfaria Occidentalis (Ugu) with 261.22ppm as being useful to stimulate heme, a necessary precursor and protein in the formation of blood in human being. Moreso, Virnonia amygdalina (ewuro) and water leaf possess anti-bacterial and anti-diabetic properties. They also provide digestive health benefits and support to the body system, including anti-inflammatory properties. Also, medicinal plant like Morinda citrifolia (Noni), which had been found to possess anti-cancer properties, has a Vitamin C amount of 528.85 mg/100g and a total carotenoids amount of 85.50 µg/g. However, despite all these results and potential utilization of these and other indigenous vegetables in Nigeria, there is a gross unawareness and/or non-cognizance of their utilization potentials, as some home garden lacks understanding of the immense nutrition benefits, thus hindering some of the populace to make proper use of these vegetables to enhance their health.

Keywords: developing countries, optimising, leafy vegetables, functional foods

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Authors: Manjusha Choudhary

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Objective: Cassia occidentalis Linn. belongs to Family Caesalpiniaceae is a common weed scattered from the foothills of Himalayas to West Bengal, South India, Burma, and Sri Lanka. It is used widely in folklore medicine in India as laxative, expectorant, analgesic, anti-malarial, hepatoprotective, relaxant, anti-inflammatory and antidiabetic. The present study was carried out to investigate the hypoglycaemic and hypolipidemic activities of ethanolic extract of Cassia occidentalis stem bark. Methods: Stem bark extract of Cassia occidentalis (SBCO) was administered orally at 250 and 500 mg/kg doses to normal and streptozotocin (STZ) induced type-2 diabetic mice. Various parameters like fasting blood glucose (FBG) level, serum cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides (TG), total protein, urea, creatinine, serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) levels and physical parameters like change in body weight, food intake, water intake were performed for the evaluation of antidiabetic effects. Results: Both the doses of extract caused a marked decrease in FBG levels in STZ induced type 2 diabetic mice. Administration of SBCO led to the decrease in the blood glucose, food intake, water intake, organ weight, SGOT, SGPT levels with significant value and increased the levels of TG, HDL cholesterol, creatinine, cholesterol, total protein with a significant value (p < 0.05-0.01). The decrease in body weight induced by STZ was restored to normal with a significant value (p < 0.01) at both doses. Conclusion: Present study reveals that SBCO possess potent hypoglycaemic and hypolipidemic activities and supports the folklore use of the stem bark of plant as antidiabetic agent.

Keywords: Cassia occidentalis, diabetes, folklore, herbs, hypoglycemia, streptozotocin

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Authors: Sunil Kumar, Uday C. Ghoshal

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Background and aims: Serotonin (5-hydroxtryptamine, 5-HT) is an important factor in gut function, playing key roles in intestinal peristalsis and secretion, and in sensory signaling in the brain-gut axis. Removal from its sites of action is mediated by a specific protein called the serotonin reuptake transporter (SERT). Polymorphisms in the promoter region of the SERT gene have effects on transcriptional activity, resulting in altered 5-HT reuptake efficiency. Functional polymorphisms may underlie disturbance in gut function in individuals suffering with disorders such as irritable bowel syndrome (IBS). The aim of this study was to assess the potential association between SERT polymorphisms and the diarrhea predominant IBS (D-IBS) phenotype Subjects: A total of 36 northern Indian female patients and 55 female northern Indian healthy controls (HC) were subjected to genotyping. Methods: Leucocyte DNA of all subjects was analyzed by polymerase chain reaction based technologies for SERT polymorphisms, specifically the insertion/deletion polymorphism in the promoter (SERT-P). Statistical analysis was performed to assess association of SERT polymorphism allele with the D-IBS phenotype. Results: The frequency of distribution of SERT-P gene was comparable between female patients with IBS and HC (p = 0.086). However, frequency of SERT-P deletion/deletion genotype was significantly higher in female patients with D-IBS compared to C-IBS and A-IBS [17/19 (89.5%) vs. 4/12 (33.3%) vs. 1/5 (20%), p=0.001, respectively]. The mucosal level of serotonin was higher in D-IBS compared to C-IBS and A-IBS [Median, range (159.26, 98.78–212.1) vs. 110.4, 67.87–143.53 vs. 92.34, 78.8–166.3 pmol/mL, p=0.001, respectively]. The mucosal level of serotonin was higher in female patients with IBS with SERT-P deletion/deletion genotype compared deletion/insertion and insertion/insertion [157.65, 67.87–212.1 vs. 110.4, 78.1–143.32 vs. 100.5, 69.1–132.03 pmol/mL, p=0.001, respectively]. Patients with D-IBS with deletion/deletion genotype more often reported symptoms of abdominal pain, discomfort (p=0.025) and bloating (p=0.039). Symptoms development following lactose ingestion was strongly associated with D-IBS and SERT-P deletion/deletion genotype (p=0.004). Conclusions: Significant association was observed between D-IBS and the SERT-P deletion/deletion genotype, suggesting that the serotonin transporter is a potential candidate gene for D-IBS in women.

Keywords: serotonin, SERT, inflammatory bowel disease, genetic polymorphism

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Authors: Mesih Kocamuftuoglu, Gonca Ozan, Enver Ozan, Nalan Kaya, Sema Temizer Ozan

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Metabolic Syndrome, one of the common metabolic disorder, occurs with co-development of insulin resistance, obesity, dislipidemia and hypertension problems. Insulin resistance appears to play a pathogenic role in the metabolic syndrome. Also, there is a relationship between insulin resistance and infertility as known. Turmeric (Curcuma longa L.) a polyphenolic chemical is widely used for its coloring, flavoring, and medicinal properties, and exhibits a strong antioxidant activity. In this study, we assess the effects of turmeric on rat uterine tissue in metabolic syndrome model induced by high fructose diet. Thirty-two adult female Wistar rats weighing 220±20 g were randomly divided into four groups (n=8) as follows; control, fructose, turmeric, and fructose plus turmeric. Metabolic syndrome was induced by fructose solution 20% (w/v) in tap water, and turmeric (C.Longa) administered at the dose of 80 mg/kg body weight every other day by oral gavage. After the experimental period of 8 weeks, rats were decapitated, serum and uterine tissues were removed. Serum lipid profile, glucose, insülin levels were measured. Uterine tissues were fixed for histological analyzes. The uterine tissue sections were stained with hematoxylin-eosin (H & E) stain, then examined and photographed on a light microscope (Novel N-800Mx20). As a result, fructose consumption effected serum lipids, insulin levels, and insulin resistance significantly. Endometrium and myometrium layers were observed in normal structure in control group of uterine tissues. Perivascular edema, peri glandular fibrosis, and inflammatory cell increase were detected in fructose group. Sections of the fructose plus turmeric group showed a significant improvement in findings when compared to the fructose group. Turmeric group cell structures were observed similar with the control group. These results demonstrated that high-fructose consumption could change the structure of the uterine tissue. On the other hand, turmeric administration has beneficial effects on uterine tissue at that dose and duration when administered with fructose.

Keywords: metabolic syndrome, rat, turmeric, uterus

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Authors: Khemakhem Nahed, Hammami Fatma, Trabelsi Houaida, Neji Sourour, Sellami Hayet, Makni Fattouma, Turki Hamida, Ayadi Ali

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Dermatophytoses are considered a public health problem and represent 10% of dermatological consultations in our region. Their epidemiology is influenced by various factors, such as lifestyle, human migration patterns, changes in the environment and the host relationship. The understanding of epidemiology has a major impact on their prevention and treatment. The aim of the study is to determine the prevalence pattern of aetiological agents and to describe the clinical characteristics of dermatophytoses between 1999 and 2019. Out of 65 059 subjects suspected to have superficial mycoses, 36 220 (55.67%) were affected with dermatophytoses. The mean age was 40.1 years (range: 10 days to 99 years). The sex ratio was 0.8. Our patients were from urban regions in 80.9% of cases. The most common type of infection was onychomycosis (42.64%), followed by tinea pedis (20.8%), intertrigo (18.3%), tinea corporis (8.48%) and tinea capitis (7.87%). The most isolated dermatophyte was Trichophyton rubrum (76.5%), followed by T. mentagrophytes complex (6.3%), Microsporum canis (5.8%), T. violaceum (5.3%), T. verrucosum (0.83%) and Epidermophyton floccosum (0.3%). Zoophilic agents have become more prevalent and their frequency has been increased from 6.46% in 1999 to 13% in 2019. It is interesting to note that M. canis has been on the rise since 2010 and it was the first etiological agent of tinea capitis (48%), while infections caused by T. violaceum continued to decrease from 1999 (16.2%) to 2019 (4.7%). Other dermatophytes have been rarely isolated: T. tonsurans (9 cases), T. schoenleinii (3 cases), T. soudanense (2 cases), M. fulvum (1 case), M. audouinii (1 case) and M. ferrugineum (2 cases).T. mentagrophytes var. quinckeanum was isolated from an inflammatory tinea capitis lesion in an a-3-year-old girl. T. mentagrophytes var. erinacei was isolated from the first case of tinea manuum, in-a-10-year-old girl. The same fungus was isolated from the hair and scales of the hedgehog. Our study showed significant changes in the dermatophytes spectrum in our region. The prevalence of zoophilic species increased in recent years due to people's behavioral changes with the adoption of pets and animal husbandry in urban settings. Molecular methods are often crucial that help us to refine the identification strains of dermatophytes and to identify their origin of the contamination.

Keywords: dermatophytoses, PCR-sequencing, spectrum, Sfax, Tunisia

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Authors: Hager Elsheikh, Juliane Glaubitz, Frank Ulrich Weiss, Matthias Sendler

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Aim: Acute pancreatitis (AP) and chronic pancreatitis (CP) are both accompanied by a prominent immune response which influences the course of disease. Whereas during AP the pro-inflammatory immune response dominates, during CP a fibroinflammatory response regulates organ remodeling. The transcription factor signal transducer and activator of transcription 6 (STAT6) is a crucial part of the Type 2 immune response. Here we investigate the role of STAT6 in a mouse model of AP and CP. Material and Methods: AP was induced by hourly repetitive i.p. injections of caerulein (50µg/kg/bodyweight) in C57Bl/6 J and STAT6-/- mice. CP was induced by repetitive caerulein injections 6 times a day, 3 days a week over 4 weeks. Disease severity was evaluated by serum amylase/lipase measurement, H&E staining of pancreas. Pancreatic infiltrate was characterized by immunofluorescent labeling of CD68, CD206, CCR2, CD4 and CD8. Pancreas fibrosis was evaluated by Azan blue staining. qRT-PCR was performed of Arg1, Nos2, Il6, Il1b, Col3a, Socs3 and Ym1. Affymetrix chip array analyses were done to illustrate the IL4/IL13/STAT6 signaling in bone marrow derived macrophages. Results: AP severity is mitigated in STAT6-/- mice, as shown by decreased serum amylase and lipase, as well as histological damage. CP mice surprisingly showed only slightly reduced fibrosis of the pancreas. Also staining of CD206 a classical marker of alternatively activated macrophages showed no decrease of M2-like polarization in the absence of STAT6. In contrast, transcription profile analysis in BMDM showed complete blockade of the IL4/IL13 pathway in STAT6-/- animals. Conclusion: STAT6 signaling pathway is protective during AP and mitigates the pancreatic damage. During chronic pancreatitis the IL4/IL13 – STAT6 axisis involved in organ fibrogenesis. Notably, fibrosis is not dependent on a single signaling pathway, and alternative macrophage activation is also complex and involves different subclasses (M2a, M2b, M2c and M2d) which could be independent of the IL4/IL13 STAT6 axis.

Keywords: chronic pancreatitis, macrophages, IL4/IL13, Type immune response

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Authors: Ishfaq A. Bukhari, Bassem Yousef Sheikh, Abdulrahman Almotrefi, Osama Yousaf, Amer Mahmood

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Olive oil is the primary source of fat in the Mediterranean diet which is associated with a low mortality for cardiovascular disease. Olive oil is rich in monounsaturated fatty acids, and has been reported for variety of beneficial cardiovascular effects including blood pressure lowering, anti-platelet, anti-diabetic and anti-inflammatory effects. Growing number evidences from preclinical and clinical studies have shown that olive oil improves insulin resistance, decrease vessels stiffness and prevent thromboembolism. We evaluated the effects of olive against streptozotocin-induced physiological disorders in the animal models of diabetes and ischemia and reperfusion (I/R)- induced cardiac arrhythmias. Diabetes was induced in male rats with a single intraperitoneal injection of streptozotocin (60 mg/kg), rats were treated for two months with olive oil (1 ml/kg p.o). Control animals received saline. Blood glucose, body weight were monitored every 14 days. At the end of the treatment rats were sacrificed hearts were isolated for mounting on langedorff’s apparatus. The blood glucose and body weight was not significantly different in the control and olive treated animals. The control diabetic animals exhibited 100% incidence of I/R –induced ventricular fibrillation which was reduced to 0% with olive oil, treatment. The duration of ventricular fibrillation reduced from 98.8± 2.3 (control) to 0 seconds in the olive oil treated group. Diltiazem, a calcium channel blocker (1 µm/L) showed similar results and protected the I/R-induced cardiac disorders. The biochemical analysis of the cardiac tissues showed that diabetes and I/R produce marked pathological changes in the cardiomyocytes including decreased glutathione (GSH) and increased oxidative stress (Malondialdehyde; MDA). Pretreatment of animals with olive oil (1 ml/kg p.o) increased GSH and MDA levels. Olive oil also improved the diabetic-induced histopathological changes in the cardiomyocytes. These finding indicates that olive possesses cardiac protective properties. Further studies are under way in our lab to explore the mechanism of the cardio-protective effect of olive oil.

Keywords: diabeties, ischemia-reperfusion, olive oil, rats heart

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Authors: Amanda C. Q. M. Vieira, Cybelly M. Melo, Camila B. M. Figueirêdo, Giovanna C. R. M. Schver, Salvana P. M. Costa, Magaly A. M. de Lyra, Ping I. Lee, José L. Soares-Sobrinho, Pedro J. Rolim-Neto, Mônica F. R. Soares

Abstract:

Epiisopiloturine (EPI) is a drug candidate that is extracted from Pilocarpus microphyllus and isolated from the waste of Pilocarpine. EPI has demonstrated promising schistosomicidal, leishmanicide, anti-inflammatory and antinociceptive activities, according to in vitro studies that have been carried out since 2009. However, this molecule shows poor aqueous solubility, which represents a problem for the release of the drug candidate and its absorption by the organism. The purpose of the present study is to investigate the extent of enhancement of kinetic solubility of a solid solution (SS) of EPI in hipromellose phthalate HP-55 (HPMCP), an enteric polymer carrier. SS was obtained by the solvent evaporation methodology, using acetone/methanol (60:40) as solvent system. Both EPI and polymer (drug loading 10%) were dissolved in this solvent until a clear solution was obtained, and then dried in oven at 60ºC during 12 hours, followed by drying in a vacuum oven for 4 h. The results show a considerable modification in the crystalline structure of the drug candidate. For instance, X-ray diffraction (XRD) shows a crystalline behavior for the EPI, which becomes amorphous for the SS. Polarized light microscopy, a more sensitive technique than XRD, also shows completely absence of crystals in SS sample. Differential Scanning Calorimetric (DSC) curves show no signal of EPI melting point in SS curve, indicating, once more, no presence of crystal in this system. Interaction between the drug candidate and the polymer were found in Infrared microscopy, which shows a carbonyl 43.3 cm-1 band shift, indicating a moderate-strong interaction between them, probably one of the reasons to the SS formation. Under sink conditions (pH 6.8), EPI SS had its dissolution performance increased in 2.8 times when compared with the isolated drug candidate. EPI SS sample provided a release of more than 95% of the drug candidate in 15 min, whereas only 45% of EPI (alone) could be dissolved in 15 min and 70% in 90 min. Thus, HPMCP demonstrates to have a good potential to enhance the kinetic solubility profile of EPI. Future studies to evaluate the stability of SS are required to conclude the benefits of this system.

Keywords: epiisopiloturine, hipromellose phthalate HP-55, pharmaceuticaltechnology, solubility

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Authors: Maha Z. Rizk, Sami A. Fattah, Heba M. Darwish, Sanaa A. Ali, Mai O. Kadry

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Although it is known that nano-TiO2 and other nanoparticles can induce liver toxicity, the mechanisms and the molecular pathogenesis are still unclear. The present study investigated some biochemical indices of nano-sized Titanium dioxide (TiO2 NPS) toxicity in mice liver and the ameliorative efficacy of individual and combined doses of idebenone, carnosine and vitamin E. Nano-anatase TiO2 (21 nm) was administered as a total oral dose of 2.2 gm/Kg daily for 2 weeks followed by the afore-mentioned antioxidants daily either individually or in combination for 1month. TiO2-NPS induced a significant elevation in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hepatic oxidative stress biomarkers [lipid peroxides (LP), and nitric oxide levels (NOX), while it significantly reduced glutathione reductase (GR), reduced glutathione (GSH) and glutathione peroxidase(GPX) levels. Moreover the quantitative RT-PCR analysis showed that nano-anatase TiO2 can significantly alter the mRNA and protein expressions of the fibrotic factors TGF-B1, VEGFand Smad-2. Histopathological examination of hepatic tissue reinforced the previous biochemical results. Our results also implied that inflammatory responses and liver injury may be involved in nano-anatase TiO2-induced liver toxicity Tumor necrosis factor-α (TNF-α) and Interleukin -6 (IL-6) and increased the percent of DNA damage which was assessed by COMET assay in addition to the apoptotic marker Caspase-3. Moreover mRNA gene expression observed by RT-PCR showed a significant overexpression in nuclear factor relation -2 (Nrf2), nuclear factor kappa beta (NF-Kβ) and the apoptotic factor (bax), and a significant down regulation in the antiapoptotic factor (bcl2) level. In conclusion idebenone, carnosine and vitamin E ameliorated the deviated previously mentioned parameters with variable degrees with the most pronounced role in alleviating the hazardous effect of TiO2 NPS toxicity following the combination regimen.

Keywords: Nano-anatase TiO2, TGF-B1, SMAD-2

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Authors: Djeddi Khaled, Houssou Hind, Miloudi Abdellatif, Rabah Siham

Abstract:

In the field of veterinary medicine, there is a growing application of artificial intelligence (AI) for diagnosing bovine mastitis, a prevalent inflammatory disease in dairy cattle. AI technologies, such as automated milking systems, have streamlined the assessment of key metrics crucial for managing cow health during milking and identifying prevalent diseases, including mastitis. These automated milking systems empower farmers to implement automatic mastitis detection by analyzing indicators like milk yield, electrical conductivity, fat, protein, lactose, blood content in the milk, and milk flow rate. Furthermore, reports highlight the integration of somatic cell count (SCC), thermal infrared thermography, and diverse systems utilizing statistical models and machine learning techniques, including artificial neural networks, to enhance the overall efficiency and accuracy of mastitis detection. According to a review of 15 publications, machine learning technology can predict the risk and detect mastitis in cattle with an accuracy ranging from 87.62% to 98.10% and sensitivity and specificity ranging from 84.62% to 99.4% and 81.25% to 98.8%, respectively. Additionally, machine learning algorithms and microarray meta-analysis are utilized to identify mastitis genes in dairy cattle, providing insights into the underlying functional modules of mastitis disease. Moreover, AI applications can assist in developing predictive models that anticipate the likelihood of mastitis outbreaks based on factors such as environmental conditions, herd management practices, and animal health history. This proactive approach supports farmers in implementing preventive measures and optimizing herd health. By harnessing the power of artificial intelligence, the diagnosis of bovine mastitis can be significantly improved, enabling more effective management strategies and ultimately enhancing the health and productivity of dairy cattle. The integration of artificial intelligence presents valuable opportunities for the precise and early detection of mastitis, providing substantial benefits to the dairy industry.

Keywords: artificial insemination, automatic milking system, cattle, machine learning, mastitis

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Authors: Rihab Gamaoun, Cynthia El Hage, Laura Ruiz, Erin Prosk, Antonio Vigano

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Introduction: Santé Cannabis (SC), a Canadian medical cannabis-specialized group of clinics based in Montreal and in the province of Québec, has served more than 5000 patients seeking cannabis-based treatment prescription for medical indications over the past five years. Within a research frame, data on the use of medical cannabis products from all the above patients were prospectively collected, leading to a large real-world database on the use of medical cannabis. The aim of this study was to gather information on the profiles of both patients and prescribed medical cannabis products at SC clinics and to assess the safety of medical cannabis among Canadian patients. Methods: Using a retrospective analysis of the database, records of 2585 patients who were prescribed medical cannabis products for therapeutic purposes between 01-November 2017 and 04-September 2019 were included. Patients’ demographics, primary diagnosis, route of administration, and chemovars recorded at the initial visits were investigated. Results: At baseline: 9% of SC patients were female, with a mean age of 57 (SD= 15.8, range= [18-96]); Cannabis products were prescribed mainly for patients with a diagnosis of chronic pain (65.9% of patients), cancer (9.4%), neurological disorders (6.5%), mood disorders (5.8 %) and inflammatory diseases (4.1%). Route of administration and chemovars of prescribed cannabis products were the following: 96% of patients received cannabis oil (51% CBD rich, 42.5% CBD:THC); 32.1% dried cannabis (21.3% CBD:THC, 7.4% THC rich, 3.4 CBD rich), and 2.1% oral spray cannabis (1.1% CBD:THC, 0.8% CBD rich, 0.2% THC rich). Most patients were prescribed simultaneously, a combination of products with different administration routes and chemovars. Safety analysis is undergoing. Conclusion: Our results provided initial information on the profile of medical cannabis products prescribed in a Canadian population and the experienced adverse events over the past three years. The Santé Cannabis database represents a unique opportunity for comparing clinical practices in prescribing and titrating cannabis-based medications across different centers. Ultimately real-world data, including information about safety and effectiveness, will help to create standardized and validated guidelines for choosing dose, route of administration, and chemovars types for the cannabis-based medication in different diseases and indications.

Keywords: medical cannabis, real-world data, safety, pharmacovigilance

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Authors: Vijaya Madhuri Devraj, Swarnalatha Guditi, Kiran Kumar Bokara, Gangadhar Taduri

Abstract:

Cell-based strategies may open therapeutic approaches that promote tolerance through manipulation of macrophages to increase long-term transplant survival rates and minimize side effects of the current immune suppressive regimens. The aim of the present study was, therefore, to test and compare the therapeutic potential of MSC and Tregs on macrophage polarization to develop an alternate cell-based treatment option in kidney transplantation. In the current protocol, macrophages from kidney transplant recipients with graft dysfunction were co-cultured with MSCs and Treg cells with and without cell-cell contact on transwell plates, further to quantitatively assess macrophage polarization in response to MSC and Treg treatment over time, M1 and M2 cell surface markers were used. Additionally, multiple soluble analytes were analyzed in cell supernatant by using bead-based immunoassays. Furthermore, to confirm our findings, gene expression analysis was done. MSCs induced the formation of M2 macrophages more than Tregs when macrophages M0 were cultured in transwell without cell contact. From this, we deduced the mechanism that soluble factors present in the MSCs condition media are involved in skewing of macrophages towards type 2 macrophages; similarly, in co-culture with cell-cell contact, MSCs resulted in more M2 type macrophages than Tregs. And an important finding of this study is the combination of both MSC-Treg showed significantly effective and consistent results in both with and without cell contact setups. Hence, it is suggestive to prefer MSCs over Tregs for secretome-based therapy and a combination of both for either therapy for effective transplantation outcomes. Our findings underline a key role of Tregs and MSCs in promoting macrophage polarization towards anti-inflammatory type. The study has great importance in prolongation of allograft and patient survival without any rejection by cell-based therapy, which induce self-tolerance and controlling infection.

Keywords: graft rejection, graft tolerance, macrophage polarization, mesenchymal stem cells, regulatory T cells, transplant immunology

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Authors: Toumi Farah, Charallah Salima

Abstract:

In the Algerian Sahara, goat farming is predominant, and it’s associated with other types of breeding, particularly camel and sheep; it also constitutes a significant proportion of breeding exclusively goat. This Saharan goat is a small ruminant with a black dress with white’s spots, hanging ears, and a coat more or less long. It is known for its hardiness and resistance to adverse conditions of arid zones and its perfect ecophysiological adaptation to harsh environmental conditions. However, pregnancy alterations, particularly abortion, degrade its productivity and cause economic losses, having both direct and indirect effects on animal production, like the costs of veterinary interventions and the reconstitution of livestock. The purpose of this work is to study the histological aspect of the liver of goats’ aborted living under nomadic herds in the region of Béni-Abbès (30° 7' N, 2° 10 'O). The organs were collected in physiological serum, rinsed, and then fixed with formaldehyde (37°, diluted at 10%). After that, these samples were processed for a topographic study. The morphometric study of the liver was performed by using an image analysis and processing software "Image J"; the various measurements obtained are intended to specify the supposed stage of development according to the body weight. The histological structure of the liver shows that the hepatic parenchyma consists of vascular conjunctive spaces surrounded by Glisson’s capsule. The sinusoids and hepatic portal vein are full of red blood cells, representing sinusoidal congestion and a thrombosed vein. At high magnification, the blood vessels show the presence of vascular thrombosis and haemorrhage in some areas of the hepatic parenchyma. Morphometric analysis shows that the number of liver parenchymal cells and the diameter of liver vessels vary according to the stage of development. The results obtained will provide details of the anatomical and cellular elements that can be used in the diagnosis of early or late abortion and late embryonic death. It would be interesting to find, by immunohistochemistry, some inflammatory markers useful for monitoring the progress of pregnancy and bioindicators of fetomaternal distress.

Keywords: aborting goat, arid zone, liver, histopathology

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Authors: Rania F. Ahmed, Sally A. El Awdan, Gehad A. Abdel Jaleel, Dalia O. Saleh, Omar A. H. Ahmed-Farid

Abstract:

The metabolic syndrome is an important public health concern often related to obesity, improper diet, and sedentary lifestyles and can predispose individuals to the development of many dangerous health conditions, disability and early death. This research aimed to investigate the efficacy of resveratrol (RSV) to reverse the neuro-complications associated with metabolic syndrome experimentally-induced in rats using an eight weeks high fat, high fructose diet (HFHF) model. The corresponding drug treatments were administered orally during the last 10 days of the diet. Behavioural tests namely the open field test (OFT) and the forced swimming test (FST) were conducted. Brain levels of monoamines viz. serotonin, norepinephrine and dopamine as well as their metabolites were assessed. 8-hydroxyguanosine (8-OHDG) as an indicative of DNA-fragmentation, nitric oxide (NOx) and tumor necrosis factor-α (TNF- α) were estimated. Finally, brain antioxidant parameters namely malondialdehyde (MDA), reduced and oxidized glutathione (GSH, GSSG) were evaluated. HFHF-induced metabolic syndrome resulted in decreased activity in the OFT and increased immobility duration in the FST. Furthermore, HFHF-induced metabolic syndrome lead to a significant increase in brain monoamines turn over as well as elevation in 8-OHDG, NOx, TNF- α, MDA and GSSG; and reduction in GSH. Ten days daily treatment with RSV (20 and 40 mg/kg p.o) dose dependently increased activity in the OFT and decreased immobility duration in the FST. Moreover, RSV normalized brain monoamines contents, reduced 8-OHDG, NOx, TNF- α, MDA and GSSG; and elevated GSH. In conclusion, we can say that RSV showed neuro-protective properties against HFHF-induced metabolic syndrome represented by monoamines preservation, prevention of neurodegeneration, anti-inflammatory and antioxidant potentials and could be recommended as a beneficial daily dietary supplement to treat the neuronal side effects associated with HFHF-induced metabolic syndrome.

Keywords: antioxidants, DNA-fragmentation, forced swimming test, HFHF-induced metabolic syndrome, monoamines, nitric oxide (NOx), open field, resveratrol, tumor necrosis factor-α (TNF- α), 8-hydroxyguanosine (8-OHDG)

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Authors: Mike T. Wei, Douglas N. Mintz, Lisa A. Mandl, Arielle W. Fein, Jayme C. Burket, Yuo-Yu Lee, Wei-Ti Huang, Vivian P. Bykerk, Mark P. Figgie, Edward F. Di Carlo, Bruce N. Cronstein, Susan M. Goodman

Abstract:

Background/Purpose: Rheumatoid arthritis (RA) patients have excellent total hip arthroplasty (THA) survival, and methotrexate (MTX), an anti-inflammatory disease modifying drug which may affect bone reabsorption, may play a role. The purpose of this study is to determine the diagnosis leading to revision THA (rTHA) in RA patients and to assess the association of radiographic lucency with MTX use. Methods: All patients with validated diagnosis of RA in the institution’s THA registry undergoing rTHA from May 2007 - February 2011 were eligible. Diagnosis leading to rTHA and medication use was determined by chart review. Osteolysis was evaluated on available radiographs by measuring maximum lucency in each Gruen zone. Differences within RA patients with/without MTX in osteolysis, demographics, and medications were assessed with chi-squared, Fisher's exact tests or Mann-Whitney U tests as appropriate. The error rate for multiple comparisons of lucency in the different Gruen zones was corrected via false discovery rate methods. A secondary analysis was performed to determine differences in diagnoses leading to revision between RA and matched OA controls (2:1 match by sex age +/- 5 years). OA exclusion criteria included presence of rheumatic diseases, use of MTX, and lack of records. Results: 51 RA rTHA were identified and compared with 103 OA. Mean age for RA was 57.7 v 59.4 years for OA (p = 0.240). 82.4% RA were female v 83.5% OA (p = 0.859). RA had lower BMI than OA (25.5 v 28.2; p = 0.166). There was no difference in diagnosis leading to rTHA, including infection (RA 3.9 v OA 6.8%; p = 0.719) or dislocation (RA 23.5 v OA 23.3%; p = 0.975). There was no significant difference in the length of time the implant was in before revision: RA 11.0 v OA 8.8 years (p = 0.060). Among RA with/without MTX, there was no difference in use of biologics (30.0 v 43.3%, p = 0.283), steroids (47.6 v 50.0%, p = 0.867) or bisphosphonates (23.8 v 33.3%, p = 0.543). There was no difference in rTHA diagnosis with/without MTX, including loosening (52.4 v 56.7%, p = 0.762). There was no significant difference in lucencies with MTX use in any Gruen zone. Patients with MTX had femoral stem subsidence of 3.7mm v no subsidence without MTX (p = 0.006). Conclusion: There was no difference in the diagnosis leading to rTHR in RA and OA, although RA trended longer prior to rTHA. In this small retrospective study, there were no significant differences associated with MTX exposure or radiographic lucency among RA patients. The significance of subsidence is not clear. Further study of arthroplasty survival in RA patients is warranted.

Keywords: hip arthroplasty, methotrexate, revision arthroplasty, rheumatoid arthritis

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Authors: Khairy M. A. Zoheir, Nehma A. Ali, Ahmed M. Darwish, Mohamed S. Kishta, Ahmed A. Abd-Rabou, Mohamed A. Abdelhafez, Karima F. Mahrous

Abstract:

The study comprehensively investigated the multifaceted therapeutic properties of the IQGAP1shRNA plasmid, encompassing its hepatoprotective, immunomodulatory, and anticancer activities. The study employed a Prednisolone-induced immunosuppressed rat model to assess the hepatoprotective and immunomodulatory effects of IQGAP1shRNA plasmid. Using this model, IQGAP1shRNA plasmid was found to modulate haematopoiesis, improving RBC, platelet, and WBC counts, underscoring its potential in hematopoietic homeostasis. Organ atrophy, a hallmark of immunosuppression in spleen, heart, liver, ovaries, and kidneys, was reversed with IQGAP1shRNA plasmid treatment, reinforcing its hepatotrophic and organotropic capabilities. Elevated hepatic biomarkers (ALT, AST, ALP, LPO) indicative of hepatocellular injury and oxidative stress were reduced with GST, highlighting its hepatoprotective and antioxidative effects. IQGAP1shRNA plasmid also restored depleted antioxidants (GSH and SOD), emphasizing its potent antioxidative and free radical scavenging capabilities. Molecular insights into immune dysregulation revealed downregulation of IQGAP1, IQGAP3 interleukin-2 (IL-2), and interleukin-4 (IL-4) mRNA expression in the liver of immunosuppressed rats. IL-2 and IL-4 play pivotal roles in immune regulation, T-cell activation, and B-cell differentiation. Notably, treatment with IQGAP1shRNA plasmid exhibited a significant upregulation of IL-2 and IL-4 mRNA expression, thereby accentuating its immunomodulatory potential in orchestrating immune homeostasis. Additionally, immune dysregulation was associated with increased levels of TNF-α. However, treatment with IQGAP1shRNA plasmid effectively decreased the levels of TNF-α, further underscoring its role in modulating inflammatory responses and restoring immune balance in immunosuppressed rats. Additionally, pharmacokinetics, bioavailability, drug-likeness, and toxicity risk assessment prediction suggest its potential as a pharmacologically favourable agent with no serious adverse effects. In conclusion, this study confirms the therapeutic potential of the IQGAP1shRNA plasmid, showcasing its effectiveness against hepatotoxicity, oxidative stress, immunosuppression, and its notable anticancer activity.

Keywords: IQGAP1, shRNA, cancer, liver, rat

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Authors: Janneth Gonzalez, Andrés Pinzon Velasco, Maria Angarita

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Astrocytes play an important role in various processes in the brain, including pathological conditions such as neurodegenerative diseases. Recent studies have shown that the increase in saturated fatty acids such as palmitic acid (PA) triggers pro-inflammatorypathways in the brain. The use of synthetic neurosteroids such as tibolone has demonstrated neuro-protective mechanisms. However, broad studies with a systemic point of view on the neurodegenerative role of PA and the neuro-protective mechanisms of tibolone are lacking. In this study, we performed the integration of multi-omic data (transcriptome and proteome) into a human astrocyte genomic scale metabolic model to study the astrocytic response during palmitate treatment. We evaluated metabolic fluxes in three scenarios (healthy, induced inflammation by PA, and tibolone treatment under PA inflammation). We also applied a control theory approach to identify those reactions that exert more control in the astrocytic system. Our results suggest that PA generates a modulation of central and secondary metabolism, showing a switch in energy source use through inhibition of folate cycle and fatty acid β‐oxidation and upregulation of ketone bodies formation. We found 25 metabolic switches under PA‐mediated cellular regulation, 9 of which were critical only in the inflammatory scenario but not in the protective tibolone one. Within these reactions, inhibitory, total, and directional coupling profiles were key findings, playing a fundamental role in the (de)regulation of metabolic pathways that may increase neurotoxicity and represent potential treatment targets. Finally, the overall framework of our approach facilitates the understanding of complex metabolic regulation, and it can be used for in silico exploration of the mechanisms of astrocytic cell regulation, directing a more complex future experimental work in neurodegenerative diseases.

Keywords: astrocytes, data integration, palmitic acid, computational model, multi-omics

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Authors: Gordana Ćetković, Vesna Tumbas Šaponjac, Jasna Čanadanović-Brunet, Sonja Đilas, Slađana Stajčić, Jelena Vulić, Mirjana Jakišić

Abstract:

Despite the recommended amount of daily intake of fruits, the consumption in modern age remains very low. Therefore there is a need for delivering valuable phytochemicals into the human body through different foods by developing functional food products fortified with natural bioactive compounds from plant sources. Recently, a growing interest rises in exploiting the fruit and vegetable by-products as sources of phytochemicals such as polyphenols, carotenoids, vitamins etc. Cherry contain high amounts of polyphenols, which are known to display a wide range of biological activities like antioxidant, anti-inflammatory, antimicrobial or anti-carcinogenic activities, improvement of vision, induction of apoptosis and neuroprotective effects. Also, cherry pomace, a by-product in juice processing, can also be promising source of phenolic compounds. However, the application of polyphenols as food additives is limited because after extraction these compounds are susceptible to degradation. Microencapsulation is one of the alternative approaches to protect bioactive compounds from degradation during processing and storage. Freeze-drying is one of the most used microencapsulation methods for the protection of thermosensitive and unstable molecules. In this study sour cherry pomace was extracted with food-grade solvent (50% ethanol) to be suitable for application in products for human use. Extracted polyphenols have been concentrated and stabilized on whey (WP) and soy (SP) proteins. Encapsulation efficiency in SP was higher (94.90%), however not significantly (p<0.05) from the one in WP (90.10%). Storage properties of WP and SP encapsulate in terms of total polyphenols, anthocyanins and antioxidant activity was tested for 6 weeks. It was found that the retention of polyphenols after 6 weeks in WP and SP (67.33 and 69.30%, respectively) was similar. The content of anthocyanins has increased in WP (for 47.97%), while their content in SP has very slightly decreased (for 1.45%) after 6-week storage period. In accordance with anthocyanins the decrease in antioxidant activity in WP (87.78%) was higher than in SP (43.02%). According to the results obtained in this study, the technique reported herewith can be used for obtaining quality encapsulates for their further use as functional food additives, and, on the other hand, for fruit waste valorization.

Keywords: cherry pomace, microencapsulation, polyphenols, storage

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Authors: Alireza Hassanshahi, Xanthe Strudwick, Zlatko Kopecki, Allison J Cowin

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Studies have shown that Flightless (Flii) is elevated in human wounds, including burns, and reducing the level of Flii is a promising approach for improving wound repair and reducing scar formation. The most effective approach has been to neutralise Flii activity using localized, intradermal application of function blocking monoclonal antibodies. However, large surface area burns are difficult to treat by intradermal injection of therapeutics, so the aim of this study was to investigate if a systemic injection of a monoclonal antibody against Flii could improve healing in mice following burn injury. Flii neutralizing antibodies (FnAbs) were labelled with Alxa-Fluor-680 for biodistribution studies and the healing effects of systemically administered FnAbs to mice with burn injuries. A partial thickness, 7% (70mm2) total body surface area scald burn injury was created on the dorsal surface of mice (n=10/group), and 100µL of Alexa-Flour-680-labeled FnAbs were injected into the intraperitoneal cavity (IP) at time of injury. The burns were imaged on days 0, 1, 2, 3, 4, and 7 using IVIS Lumina S5 Imaging System, and healing was assessed macroscopically, histologically, and using immunohistochemistry. Fluorescent radiance efficiency measurements showed that IP injected Alexa-Fluor-680-FnAbs localized at the site of burn injury from day 1, remaining there for the whole 7-day study. The burns treated with FnAbs showed a reduction in macroscopic wound area and an increased rate of epithelialization compared to controls. Immunohistochemistry for NIMP-R14 showed a reduction in the inflammatory infiltrate, while CD31/VEGF staining showed improved angiogenesis post-systemic FnAb treatment. These results suggest that systemically administered FnAbs are active within the burn site and can improve healing outcomes. The clinical application of systemically injected Flii monoclonal antibodies could therefore be a potential approach for promoting the healing of large surface area burns immediately after injury.

Keywords: biodistribution, burn, flightless, systemic, fnAbs

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Authors: S. Koppikar, P. Kulkarni, D. Ingale , N. Wagh, S. Deshpande, A. Mahajan, A. Harsulkar

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Crucial role of reactive oxygen species (ROS) in the progression Osteoarthritis (OA) pathogenesis has been endorsed several times though its exact mechanism remains unclear. Oxidative stress is known to instigate classical stress factors such as cytokines, chemokines and ROS, which hampers cartilage remodelling process and ultimately results in worsening the disease. Synovial fluid (SF) is a biological communicator between cartilage and synovium that accumulates redox and biochemical signalling mediators. The present work attempts to measure several oxidative stress markers in the synovial fluid obtained from knee OA patients with varying degree of disease severity. Thirty OA and five Meniscal-tear (MT) patients were graded using Kellgren-Lawrence scale and assessed for Nitric oxide (NO), Nitrate-Nitrite (NN), 2,2-diphenyl-1-picrylhydrazyl (DPPH), Ferric Reducing Antioxidant Potential (FRAP), Catalase (CAT), Superoxide dismutase (SOD) and Malondialdehyde (MDA) levels for comparison. Out of various oxidative markers studied, NO and SOD showed significant difference between moderate and severe OA (p= 0.007 and p= 0.08, respectively), whereas CAT demonstrated significant difference between MT and mild group (p= 0.07). Interestingly, NN revealed statistically positive correlation with OA severity (p= 0.001 and p= 0.003). MDA, a lipid peroxidation by-product was estimated maximum in early OA when compared to MT (p= 0.06). However, FRAP did not show any correlation with OA severity or MT control. NO is an essential bio-regulatory molecule essential for several physiological processes, and inflammatory conditions. However, due to its short life, exact estimation of NO becomes difficult. NO and its measurable stable products are still it is considered as one of the important biomarker of oxidative damage. Levels of NO and nitrite-nitrate in SF of patients with OA indicated its involvement in the disease progression. When SF groups were compared, a significant correlation among moderate, mild and MT groups was established. To summarize, present data illustrated higher levels of NO, SOD, CAT, DPPH and MDA in early OA in comparison with MT, as a control group. NN had emerged as a prognostic bio marker in knee OA patients, which may act as futuristic targets in OA treatment.

Keywords: antioxidant, knee osteoarthritis, oxidative stress, synovial fluid

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Authors: Mansi Patel, Priti Mehta

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Background: Ionizing radiations have detrimental effects on humans, and the growing technological encroachment has increased human exposure to it enormously. So, the safety issues have emphasized researchers to develop radioprotector from natural resources having minimal toxicity. A substance having anti-inflammatory, antioxidant, and immunomodulatory activity can be a potential candidate for radioprotection. One such plant with immense potential i.e. Bamboo was selected for the present study. Purpose: The study aims to evaluate the potential of Indian bamboo leaves for protection against the clastogenic effect of gamma radiation. Methods: The protective effect of bamboo leaf extract against gamma radiation-induced genetic damage in human peripheral blood lymphocytes (HPBLs) was evaluated in vitro using Cytokinesis blocked micronuclei assay (CBMN). The blood samples were pretreated with varying concentration of extract 30 min before the radiation exposure (4Gy & 6Gy). The reduction in the frequency of micronuclei was observed for the irradiated and control groups. The effect of various concentration of bamboo leaf extract (400,600,800 mg/kg) on the development of radiation induced sickness and altered mortality in mice exposed to 8 Gy of whole-body gamma radiation was studied. The developed symptoms were clinically scored by multiple endpoints for 30 days. Results: Treatment of HPBLs with varying concentration of extract before exposure to a different dose of γ- radiation resulted in significant (P < 0.0001) decline of radiation induced micronuclei. It showed dose dependent and concentration driven activity. The maximum protection ~ 70% was achieved at nine µg/ml concentration. Extract treated whole body irradiated mice showed 50%, 83.3% and 100% survival for 400, 600, and 800mg/kg with 1.05, 0.43 and 0 clinical score respectively when compared to Irradiated mice having 6.03 clinical score and 0% survival. Conclusion: Our findings indicate bamboo leaf extract reduced the radiation induced cytogenetic damage. It has also increased the survival ratio and reduced the radiation induced sickness and mortality when exposed to a lethal dose of gamma radiation.

Keywords: bamboo leaf extract, Cytokinesis blocked micronuclei (CBMN) assay, ionizing radiation, radio protector

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

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

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

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