Search results for: chronic inflammatory diseases

Authors: Priyanka Sharma, Niti Puri

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Anemia develops when blood lacks enough healthy erythrocytes. Past studies indicated that anemia, inflammatory process, and oxidative stress are interconnected. Erythrocytes are continuously exposed to reactive oxygen species (ROS) during circulation, due to normal aerobic cellular metabolism and also pathology of inflammatory diseases. Systemic mastocytosis and genetic depletion of mast cells have been shown to affect anaemia. In the present study, we attempted to reveal whether mast cells have a direct role in clearance or erythrophagocytosis of normal or oxidatively damaged erythrocytes. Murine erythrocytes were treated with tert-butyl hydroperoxidase (t-BHP), an agent that induces oxidative damage and mimics in vivo oxidative stress. Normal and oxidatively damaged erythrocytes were labeled with carboxyfluorescein succinimidyl ester (CFSE) to track erythrophagocytosis. We show, for the first time, direct erythrophagocytosis of oxidatively damaged erythrocytes in vitro by RBL-2H3 mast cells as well as in vivo by murine peritoneal mast cells. Also, activated mast cells, as may be present in inflammatory conditions, showed a significant increase in the uptake of oxidatively damaged erythrocytes than resting mast cells. This suggests the involvement of mast cells in erythrocyte clearance during oxidative stress or inflammatory disorders. Partial inhibition of phagocytosis by various inhibitors indicated that this process may be controlled by several pathways. Hence, our study provides important evidence for involvement of mast cells in severe anemia due to inflammation and oxidative stress and might be helpful to circumvent the adverse anemic disorders.

Keywords: mast cells, anemia, erythrophagocytosis, oxidatively damaged erythrocytes

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Authors: R. N. Nataria, A. D. Paryuni, R. Wasito

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Layer farms in Indonesia have still obstacles to increasing their productivity, especially due to poultry diseases. The red onion (Allium ascalonicum L.) is a plant that contains flavonoid and saponin. Flavonoid is useful as anti-inflammatory and antioxidant while saponin is useful as antivirus, anti-inflammatory, antifungal, and immunomodulator. This study aimed to know and determine the effect of onion extracts to pulmonary histopathological lesions in layer chickens which raised in the battery cage. This study used eighteen layer chickens at seventeen days old. The eighteen layer chickens were divided into three groups of six each, namely without administration of red onion extract (Group I), with administration red onion extract through drinking water (Group II) and with administration red onion extract peroral (Group III). Every ten days, six chickens were necropsied and then the lungs were processed for histopathological preparations and stained with routine hematoxylin and eosin. The results showed that the lungs of the Group I had severe congestion and diffuse hemorrhages. In Group II, lungs had moderate congestion and hemorrhages. In group III, lungs had mild congestion and hemorrhages. It is concluded, that red onion extract apparently has reduced the lungs lesions in layer chickens.

Keywords: histopathological lesions, layers, lungs, poultry diseases, red onion extract

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Authors: Ashit Syngle, Inderjit Verma, Pawan Krishan

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Therapeutic approaches used previously relied on disease-modifying antirheumatic drugs (DMARDs) that had only partial clinical benefit and were associated with significant toxicity. Spironolactone, an oral aldosterone antagonist, suppresses inflammatory mediators. Clinical efficacy of spironolactone compared with placebo in patients with active psoriatic arthritis despite treatment with prior traditional DMARDs. In the 24-week, placebo-controlled study patients (n=31) were randomized to placebo and spironolactone (2 m/kg/day). Patients on background concurrent DMARDs continued stable doses (methotrexate, leflunomide, and/or sulfasalazine). Primary outcome measures were the assessment of disease activity measures i.e. 28-joint disease activity score (DAS28) and diseases activity in psoriatic arthritis (DAPSA) at week 24. The key secondary endpoint was change from baseline in Health Assessment Questionnaire–Disability Index (HAQ-DI) at week 24. Additional efficacy outcome measures at week 24 included improvements in the markers of inflammation (ESR and CRP) and pro-inflammatory cytokines TNF-α, IL-6 and IL-1. At week 24, spironolactone significantly reduced disease activity measure DAS-28 (p<0.001) and DAPSA (p=0.001) compared with placebo. Significant improvements in key secondary measures HAQ-DI (disability index) were evident with spironolactone (p=0.02) versus placebo. After week 24, there was significant reduction in pro-inflammatory cytokines level TNF-α, IL-6 (p<0.01) as compared with placebo group. However, there was no significant improvement in IL-1 in both treatment and placebo groups. There were minor side effects which did not mandate stopping of spironolactone. No change in any biochemical profile was noted after spironolactone treatment. Spironolactone was effective in the treatment of PsA, improving disease activity, physical function and suppressing the level of pro-inflammatory cytokines. Spironolactone demonstrated an acceptable safety profile and was well tolerated.

Keywords: spironolactone, inflammation, inflammatory cytokine, psoriatic arthritis

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Authors: Joon Hock Yeo, Munirah Ismail

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Chronic venous insufficiency is a condition where the venous wall or venous valves fail to operate properly. As such, it is difficult for the blood to return from the lower extremities back to the heart. Chronic venous insufficiency affects many people worldwide. In last decade, there have been many new and innovative designs of prosthetic venous valves to replace the malfunction native venous valves. However, thus far, to the authors’ knowledge, there is no successful prosthetic venous valve. In this project, we have developed a venous valve which could operate under low pressure. While further testing is warranted, this unique valve could potentially alleviate problems associated with chronic venous insufficiency.

Keywords: prosthetic venous valve, bi-leaflet valve, chronic venous insufficiency, valve hemodynamics

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Authors: Jeong-Hyun Hong, Wonsuk Choi, Hyungdal Park, Jinseok Kim, Junesun Kim

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Identifying the chronic functions of an implanted neural electrode is an important factor in acquiring neural signals through the electrode or restoring the nerve functions after peripheral nerve injury. The purpose of this study was to investigate the biocompatibility of the chronic implanted neural electrode into the sciatic nerve. To do this, a sieve-type neural electrode was implanted at proximal and distal ends of a transected sciatic nerve as an experimental group (Sieve group, n=6), and the end-to-end epineural repair was operated with the cut sciatic nerve as a control group (reconstruction group, n=6). All surgeries were performed on the sciatic nerve of the right leg in Sprague Dawley rats. Behavioral tests were performed before and 1, 4, 7, 10, 14, and weekly days until 5 months following surgery. Changes in sensory function were assessed by measuring paw withdrawal responses to mechanical and cold stimuli. Motor function was assessed by motion analysis using a Qualisys program, which showed a range of motion (ROM) related to the joints. Neurofilament-heavy chain and fibronectin expression were detected 5 months after surgery. In both groups, the paw withdrawal response to mechanical stimuli was slightly decreased from 3 weeks after surgery and then significantly decreased at 6 weeks after surgery. The paw withdrawal response to cold stimuli was increased from 4 days following surgery in both groups and began to decrease from 6 weeks after surgery. The ROM of the ankle joint was showed a similar pattern in both groups. There was significantly increased from 1 day after surgery and then decreased from 4 days after surgery. Neurofilament-heavy chain expression was observed throughout the entire sciatic nerve tissues in both groups. Especially, the sieve group was showed several neurofilaments that passed through the channels of the sieve-type neural electrode. In the reconstruction group, however, a suture line was seen through neurofilament-heavy chain expression up to 5 months following surgery. In the reconstruction group, fibronectin was detected throughout the sciatic nerve. However, in the sieve group, the fibronectin was observed only in the surrounding nervous tissues of an implanted neural electrode. The present results demonstrated that the implanted sieve-type neural electrode induced a focal inflammatory response. However, the chronic implanted sieve-type neural electrodes did not cause any further inflammatory response following peripheral nerve injury, suggesting the possibility of the chronic application of the sieve-type neural electrodes. This work was supported by the Basic Science Research Program funded by the Ministry of Science (2016R1D1A1B03933986), and by the convergence technology development program for bionic arm (2017M3C1B2085303).

Keywords: biocompatibility, motor functions, neural electrodes, peripheral nerve injury, sensory functions

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Authors: Sandeep Pandey, Nimra Habib, Ranjana Singh, Abbas Ali Mahdi

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Leukemia is a malignancy of blood that mainly affects children and young adults; while advancement in the early diagnosis will have the potential to improve the outcome of diseases. A wide range of disease including leukemia shows inflammatory signals in their pathogenesis. In a pilot study conducted in our laboratory, 52 people were screened, of which 26 had leukemia and 26 were free from any kind of malignancy. We performed the estimation of the inflammatory cytokine Interleukin-8 and it was found significantly raised in all the leukemia patients concerning healthy volunteers who participated in the study. Flow cytometry had been performed for the confirmation of leukemia and further genomic, and proteomic, analyses of the sample revealed that IL-8 levels showed a positive correlation in patients with leukemia. The results had shown constitutive secretion of interleukin-8 by leukemia cells. So, our finding demonstrated that IL-8 is considered to have a role in the pathogenesis of leukemia, and quantification of IL-8 levels in leukemia conditions might be more useful and feasible in the clinical setting for the prediction of drug responses where it may represent a putative target for innovative diagnostic toward effective therapeutic approaches. However, further research explorations in this area are needed that include a greater number of patients with all different forms of leukemia, and estimating their IL-8 levels may hold the key for the additional predictive values on the recurrence of leukemia and its prognosis.

Keywords: T-ALL, IL-8, leukemia pathogenesis, cancer therapeutics

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Authors: Mahshid Rezaei, Zahra Tajari, Zahra Esmaeily, Atefeh Eyvazkhani, Shahrzad Daei, Marjan Mansouri Dara, Mohaddesh Rezaei, Abolghassem Djazayeri, Ahmadreza Dorosti Motlagh

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Background: Musculoskeletal pain is one of the most prevalent symptoms in elderly age. Nutrition and diet are considered important underlying factors that could affect chronic musculoskeletal pain. The purpose of this study was to identify the relationship between empirical dietary inflammatory patterns (EDII) and musculoskeletal pain. Method: In this cross-sectional study, 213 elderly individuals were selected from several health centers. The usual dietary intake was evaluated by a valid and reliable 147-items food frequency questionnaire (FFQ). To measure the intensity of pain, Visual Analogue Scale (VAS) was used. Multiple Linear Regression was applied to assess the association between EDII and musculoskeletal pain. Results: The results of multiple linear regression analysis indicate that a higher EDII score was associated with higher musculoskeletal pain (β= 0.21: 95% CI: 0.24-1.87: P= 0.003). These results stayed significant even after adjusting for covariates such as sex, marital status, height, family number, sleep, BMI, physical activity duration, waist circumference, protector, and medication use (β= 0.16: 95% CI: 0.11-1.04: P= 0.02). Conclusion: Study findings indicated that higher inflammation of diet might have a direct association with musculoskeletal pains in elderlies. However, further investigations are required to confirm these findings.

Keywords: musculoskeletal pain, empirical dietary inflammatory pattern, elderlies, dietary pattern

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Authors: Orestis Kasinopoulos, Maria Karekla, Vasilis Vasiliou, Evangelos Karademas

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Acceptance and Commitment Therapy (ACT) is an empirically supported intervention for treating Chronic Pain Patients, yet its effectiveness for some chronic conditions or when adapted to other languages, has not been explored. An ACT group intervention was designed to explore the effectiveness of treating a Greek speaking heterogeneous sample of Chronic Pain patients with the aim of increasing quality of life, acceptance of pain and functionality. Sixty-nine patients were assessed and randomly assigned to an ACT or control group (relaxation techniques) for eight, 90-minute, sessions. Results are currently being analysed and follow-ups (6 and 12 month) are being completed. Low adherence rates and high attrition rates observed in the study, however point to the direction of future modified interventions. Such modifications may include web-based and smartphone interventions and their benefits in being implemented in chronic pain patients.

Keywords: chronic pain, ACT, internet-delivered, digitalised intervention, adherence, attrition

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Authors: Hyun-Ju Oh, Soon-Rim Suh, Mihan Kim

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The steady and rapid increase of the older population is a global phenomenon. Chronic diseases and disabilities are increased due to aging. In general, exercise has been known to be most effective in preventing and managing chronic back pain. However, it is hard for the older women to initiate and maintain the exercise. Transtheoretical model (TTM) is one of the theories explain behavioral changes such as exercise. The application of the program considering the stage of behavior change is effective for the elderly woman to start and maintain the exercise. The purpose of this study was to develop TTM based exercise program and to examine its effect for elderly women with chronic back-pain. For the program evaluation, the non-equivalent control pre-posttest design was applied. The independent variable of this study is exercise intervention program. The contents of the program were constructed considering the characteristics of the elderly women with chronic low back pain, focusing on the process of change, the stage of change by the previous studies. The developed exercise program was applied to the elderly women with chronic low back pain in the planning stage and the preparation stage. The subjects were 50 older women over 65 years of age with chronic back-pain who did not practice regular exercise. The experimental group (n=25) received the 8weeks TTM based exercise program. The control group received the book which named low back pain management. Data were collected at three times: before the exercise intervention, right after the intervention, and 4weeks after the intervention. The dependent variables were the processes of change, decisional balance, exercise self-efficacy, back-pain, depression and muscle strength. The results of this study were as follows. Processes of change (<.001), pros of decisional balance (<.001), exercise self-efficacy (<.001), back pain (<.001), depression (<.001), muscle strength (<.001) were higher in the experimental group than in the control group right after the program and 4weeks after the programs. The results of this study show that applying the TTM based exercise program increases the use of the change process, increases the exercise self-efficacy, increases the stage of changing the exercise behavior and strengthens the muscular strength by lowering the degree of pain and depression Respectively. The significance of the study was to confirm the effect of continuous exercise by maintaining regular exercise habits by applying exercise program of the transtheoretical model to the chronic low back pain elderly with exercise intention.

Keywords: chronic back pain, elderly, exercise, women

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Authors: Williams A. Adu, Cynthia A. Danquah, Paul P. S. Ossei, Selase Ativui, Michael Ofori, James Asenso, George Owusu

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Background Silicosis is an occupational disease of the lung that is caused by chronic exposure to silica dust. There is a higher frequency of co-existence of silicosis with tuberculosis (TB), ultimately resulting in lung fibrosis and respiratory failure. Chronic intake of synthetic drugs has resulted in undesirable side effects. Diosgenin is a steroidal saponin that has been shown to exert a therapeutic effect on lung injury. Therefore, we investigated the ability of diosgenin to reduce the susceptibility of silica-induced TB in rats. Method Silicosis was induced by intratracheal instillation of 50 mg/kg crystalline silica in Sprague Dawley rats. Different doses of diosgenin (1, 10, and 100 mg/kg), Mycobacterium smegmatis and saline were administered for 30 days. Afterwards, 5 of the rats from each group were sacrificed, and the 5 remaining rats in each group, except the control, received Mycobacterium smegmatis. Treatment of diosgenin continued until the 50th day, and the rats were sacrificed at the end of the experiment. The result was analysed using a one-way analysis of variance (ANOVA) with a Graph-pad prism Result At a half-maximal inhibition concentration of 48.27 µM, diosgenin inhibited the growth of Mycobacterium smegmatis. There was a marked decline in the levels of immune cell infiltration and cytokines production. Lactate dehydrogenase and total protein levels were significantly reduced compared to control. There was an increase in the survival rate of the treatment group compared to the control. Conclusion Diosgenin ameliorated silica-induced pulmonary tuberculosis by declining the levels of inflammatory and pro-inflammatory cytokines and, in effect, significantly reduced the susceptibility of rats to pulmonary TB.

Keywords: silicosis, tuberculosis, diosgenin, fibrosis, crystalline silica

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Authors: S. Fazelifar, M. Ghasemi

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Aim: Recent studies on cardiovascular risk factors have been focused on the new markers of inflammatory diseases such as C-reactive protein (CRP). Research evidence shows that physical activity along with other factors such as reduced smoking, controlling blood pressure, control blood lipids TC, LDL-c, HDL-c and having a healthy weight can reduce the risk of chronic heart disease (CHD) .Therefore, the aim of this study was to determine the effect of twelve weeks aerobic exercise and consumption of apple vinegar on cardiovascular risk factor in older women. Methodology: 28 inactive women (mean body weight 72.13 ± 8.6 kg, height 157 ± 7.4cm, age 48.06 ± 5.18 years and BMI 28.2 ± 3.2 kg/m2) by recall and notice of investigation, among of the eligible voters recruited and randomly divided in 4 groups: control, apple vinegar, exercise, exercise + apple vinegar. The training program includes a 20-minute warm-up and stretching, running for 15 minutes in the first session with an intensity of 80% of maximum heart rate and an increase in one-minute run time in next training session. Also, subjects in experimental groups received daily specified amount of 50 ml apple vinegar. Blood samples were collected from the brachial vein in before and after training to measure CRP and blood lipids (cholesterol, HDL, VLDL, LDL). The levels of CRP were measured by ELISA way. K-S test to determine the normality of the data and analysis of variance for repeated measures was used to analyze the data. A significant difference in the p < 0/05 accepted. Results: The results indicated that individual characteristics including height, weight, age, and body mass index were not significantly different among the four groups. The results showed that levels of CRP and LDL cholesterol were significantly reduced in all groups at post-test compared to the pre-test. The HDL levels increased significantly in all groups in post-test compared to the pre-test. Analysis of the data indicates that levels of CRP, TC, and LDL were significantly reduced in all groups compared to the control group, while the changes in the other groups were not significant relative to each other. Conclusion: Results of this study showed that twelve weeks of aerobic exercise with apple vinegar cause a significant decrease in CRP, cholesterol, LDL, and significantly increased HDL levels. According to the results of this study, it is possible that aerobic exercise with apple vinegar can inhibit CRP and undesirable fats. Considering the strong association between the inflammatory indices and the prevalence of cardiovascular diseases, every factor that decreases these indices can reduce the cardiovascular complications.

Keywords: aerobic exercise, apple vinegar, CRP, older women

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Authors: Sahar Iqrar, Malik Adeel Anwar, Zain Akram, Maria Noor

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Introduction: Oral lichen planus is a chronic inflammatory condition of unknown etiology. Oral lichen planus may be related with several other diseases. Grinspan's Syndrome is characterized by a triad of oral lichen planus, hypertension, and diabetes mellitus. Other associations reported in the literature are with chronic liver disease and, with dyslipidemia. The nature of these associations is still not fully understood. Material and methods: Study was conducted in Department of Oral Medicine, Fatima Memorial Hospital College of Medicine and Dentistry, Lahore, Pakistan. A total of n=89 clinically diagnosed patients of oral lichen planus of both gender and all age groups were recruited and detailed history were recorded in the designed performs. Results: A total of n=89 patients were taken with male to female ratio of 3:8 in which 24 were male and 65 females. Mean age was 48.8 ± 13.8 years. Age range of 10-74 years was seen. Among these patients suffering from oral lichen planus, 41.6% (n=37) had a positive history for hypertension with 59.5% (n=22) of these patients were taking different medication for their condition. Whereas Diabetes Mellitus was found in 24.7% (n=22) patients with 72.7% (n=16) of these patients using the hypoglycemic drug (oral or injectable) to control their blood glucose levels. Out of these n=89 lichen planus patients 21.3% had both hypertension and diabetes mellitus (fulfilling the criteria for Grinspan's Syndrome). Out of this Grinspan's Syndrome pool 94.7% (n=19) were taking drug atleast for one of the two conditions. Conclusion: As noticed form the medical history of the patients, most of them were using hypoglycemic drugs for diabetes mellitus and beta blockers, diuretics and calcium channel blockers for hypertension. These drugs are known for lichenoid reaction. Therefore, it should be ruled out at histopathological/ immunological and molecular level whether these patients are suffering from lichen planus or lichenoid drug reaction to truly declare them as patients with Grinspan’s Syndrome.

Keywords: diabetes mellitus, grinspan's syndrome, lichenoid drug reaction, oral lichen planus

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Authors: Mustafa M. Donma, Erkut Karasu, Burcu Ozdilek, Burhan Turgut, Birol Topcu, Burcin Nalbantoglu, Orkide Donma

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The mechanisms underlying the association between obesity and asthma may be related to a decreased immunological tolerance induced by a defective function of regulatory T cells (Tregs). The aim of this study is to establish the potential link between these diseases and CD4+, CD25+ FoxP3+ Tregs as well as T helper cells (Ths) in children. This is a prospective case control study. Obese (n:40), asthmatic (n:40), asthmatic obese (n:40), and healthy children (n:40), who don't have any acute or chronic diseases, were included in this study. Obese children were evaluated according to WHO criteria. Asthmatic patients were chosen based on GINA criteria. Parents were asked to fill up the questionnaire. Informed consent forms were taken. Blood samples were marked with CD4+, CD25+ and FoxP3+ in order to determine Tregs and Ths by flow cytometric method. Statistical analyses were performed. p≤0.05 was chosen as meaningful threshold. Tregs exhibiting anti-inflammatory nature were significantly lower in obese (0,16%; p≤0,001), asthmatic (0,25%; p≤0,01) and asthmatic obese (0,29%; p≤0,05) groups than the control group (0,38%). Ths were counted higher in asthma group than the control (p≤0,01) and obese (p≤0,001)) groups. T cell immunity plays important roles in obesity and asthma pathogeneses. Decreased numbers of Tregs found in obese, asthmatic and asthmatic obese children may help to elucidate some questions in pathophysiology of these diseases. For HOMA-IR levels, any significant difference was not noted between control and obese groups, but statistically higher values were found for obese asthmatics. The values obtained in all groups were found to be below the critical cut off points. This finding has made the statistically significant difference observed between Tregs of obese, asthmatic, obese asthmatic, and control groups much more valuable. These findings will be useful in diagnosis and treatment of these disorders and future studies are needed. The production and propagation of Tregs may be promising in alternative asthma and obesity treatments.

Keywords: asthma, flow cytometry, pediatric obesity, T cells

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Authors: Aysegul Alyamac, Sukru Gulec

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Ankaferd Blood Stopper (ABS) is a plant extract used to stop bleeding caused by injuries and surgical interventions. ABS also involved in wound healing of intestinal mucosal damage due to oxidative stress and inflammation. Inflammatory Bowel Disease (IBD) is a common chronic disorder of the gastrointestinal tract that causes abdominal pain, diarrhea, and gastrointestinal bleeding, and increases the risk of colon cancer. Inflammation is an essential factor in the development of IBD. The various studies have been performed about the physiological effects of ABS; however, ABS dependent mechanism on colonic inflammation has not been elucidated. Thus, the protective effect of ABS on colonic inflammation was investigated in this study. The Caco-2 and RAW 264.7 murine macrophage cells were used as a model of in vitro colonic inflammation. RAW 264.7 cells were treated with lipopolysaccharide (LPS) for 12 hours to induce the inflammation, and a conditional medium was obtained. Caco-2 cells were treated with 15 µl/ml ABS for 4 hours, then incubated with conditional medium and the cells also were incubated with 15 µl/ml ABS and conditional medium together for 4 hours. Tumor necrosis factor alpha (TNF-α) protein levels were targeted in testing inflammatory condition and its level was significantly increased (25 fold, p<0.001) compared to the control group by using Enzyme-Linked Immunosorbent Assay (ELISA) method. The COX-2 mRNA level was used as a marker gene to show the possible anti-inflammatory effect of ABS in Caco-2 cells. RAW cells-derived conditional medium significantly (3.3 fold, p<0.001) induced cyclooxygenase-2 (COX-2) mRNA levels in Caco-2 cells. The pretreatment of Caco-2 cells caused a significant decrease (3.3 fold, p<0.001) in COX-2 mRNA levels relative to conditional medium given group. Furthermore, COX-2 mRNA level was significantly reduced (4,7 fold, p<0.001) in ABS and conditional medium treated group. These results suggest that ABS might have an anti-inflammatory effect in vitro.

Keywords: Ankaferd blood stopper, CaCo-2, colonic inflammation, RAW 264.7

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Authors: Kristina De Milt, Nicole Huang, Jihye Park

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Opioids have been a mainstay of the treatment of chronic pain, but their overprescription and misuse have led to an opioid epidemic. Recently, as an attempt to decrease the number of opioids prescribed, the use of cannabinoid therapy has become an increasingly popular adjunctive chronic pain management choice among providers. This review of literature investigates the effects of adjunctive cannabinoids to opioids in the management of chronic pain. The nine articles are included in the literature review range from observational studies to meta-analyses published in the year 2016 and after. A majority of the studies showed a decrease in the need for opioids after adjunctive cannabinoids were introduced and, in some instances, the cessation of opioid consumption. More high-quality evidence is needed to further support this stance and providers should weigh the benefits and risks of adjunctive cannabinoids according to the clinical picture.

Keywords: cannabis, chronic pain, opioids, pain management

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Authors: Hakim Chayeb

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Macrophages (Mo) play an essential role in host defense against pathogens. These inflammatory cells contain a large group of inducible enzymes such as NO synthase (NOS). This study was conducted to characterize experimentally induced inflammation in vivo by lipopolysaccharides (LPS). LPS is an essential component of the outer membrane of Gram-negative bacteria and a potent inducer of macrophage. Except control rats, all rats received different doses of LPS intra-peritoneally. The involvement of inducible NO synthase (iNOS) and constitutive (cNOS ) in the modulation of the inflammatory response was studied by treating the rats with L-NAME (non-selective NOS inhibitor) or aminoguanidine (AG inhibitor of iNOS). Inhibitors were injected 24 hours before LPS administration. The results showed that esterase activity (a marker of macrophage infiltration) which is induced by LPS is reduced by AG, was potentiated by treatment with L-NAME in tissue homogenates of the liver, kidney and spleen. Meanwhile, the concentrations of nitric oxide (NO) induced by LPS were reduced with AG and are completely inhibited with L-NAME in the tissues studied. NO concentrations and plasma transaminase levels have undergone remarkable increases in rats treated with LPS alone. However, the AG significantly reduced these rates. Our results highlighted the role of NO synthase inhibitors in reducing of inflammatory responses that characterize many infectious diseases.

Keywords: aminoguanidine, esterase, LPS, L-NAME, macrophage, nitric oxide

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Authors: Rayhana Begum, Manju Sharma

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Careya arborea Roxb. belongs to the Lecythidaceae family, is traditionally used in tumors, anthelmintic, bronchitis, epileptic fits, astringents, inflammation, an antidote to snake-venom, skin disease, diarrhea, dysentery with bloody stools, dyspepsia, ulcer, toothache, and ear pain. The present study was focused on investigating the anti-arthritic effect of coumaroyl lupendioic acid, a new lupane-type triterpene from Careya arborea stem bark in the chronic inflammatory model and further assessing its possible mechanism on the modulation of inflammatory biomarkers. Arthritis was induced by injecting 0.1 ml of Complete Freund’s Adjuvant (5 mg/ml of heat killed Mycobacterium tuberculosis) into the subplantar region of the left hind paw. Treatment with coumaroyl lupendioic acid (10 and 20 mg/kg, p.o.) and reference drugs (indomethacin and dexamethasone at the dose of 5 mg/kg, p.o.) were started on the day of induction and continued up to 28 days. The progression of arthritis was evaluated by measuring paw volume, tibio tarsal joint diameters, and arthritic index. The effect of coumaroyl lupendioic acid (CLA) on the production PGE₂, NO, MPO, NF-κB, TNF-α, IL-1β, and IL-6 on serum level as well as inflamed paw tissue were also assessed. In addition, ankle joints and spleen were collected and prepared for histological examination. CLA in inflamed rats resulted in significant amelioration of paw edema, tibio-tarsal joint swelling and arthritic score as compared to CFA control group. The results indicated that CLA treated groups markedly decreased the levels of inflammatory mediators (PGE₂, NO, MPO and NF-κB levels) and down-regulated the production of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in paw tissue homogenates as well as in serum. However, the more pronounced effect was observed in the inflamed paw tissue homogenates. CLA also revealed a protective effect to the tibio-tarsal joint cartilage and spleen. These results suggest that coumaroyl lupendioic acid inhibits inflammation may be through the suppression of the cascade of proinflammatory mediators via the down-regulation of NF-ҡB.

Keywords: complete Freund’s adjuvant , Coumaroyl lupendioic acid, pro-inflammatory cytokines, prostaglandin E2

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Authors: Jyoti Singh, Ranju Bansal

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Fighting pain and inflammation is a common problem faced by physicians while dealing with a wide variety of diseases. Since ancient time nonsteroidal anti-inflammatory agents (NSAIDs) and opioids have been the cornerstone of treatment therapy, however, the usefulness of both these classes is limited due to severe side effects. NSAIDs, which are mainly used to treat mild to moderate inflammatory pain, induce gastric irritation and nephrotoxicity whereas opioids show an array of adverse reactions such as respiratory depression, sedation, and constipation. Moreover, repeated administration of these drugs induces tolerance to the analgesic effects and physical dependence. Further discovery of selective COX-2 inhibitors (coxibs) suggested safety without any ulcerogenic side effects; however, long-term use of these drugs resulted in kidney and hepatic toxicity along with an increased risk of secondary cardiovascular effects. The basic approaches towards inflammation and pain treatment are constantly changing, and researchers are continuously trying to develop safer and effective anti-inflammatory drug candidates for the treatment of different inflammatory conditions such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, psoriasis and multiple sclerosis. Synthetic 3(2H)-pyridazinones constitute an important scaffold for drug discovery. Structure-activity relationship studies on pyridazinones have shown that attachment of a lactam at N-2 of the pyridazinone ring through a methylene spacer results in significantly increased anti-inflammatory and analgesic properties of the derivatives. Further introduction of the heterocyclic ring at lactam nitrogen results in improvement of biological activities. Keeping in mind these SAR studies, a new series of compounds were synthesized as shown in scheme 1 and investigated for anti-inflammatory, analgesic, anti-platelet activities and docking studies. The structures of newly synthesized compounds have been established by various spectroscopic techniques. All the synthesized pyridazinone derivatives exhibited potent anti-inflammatory and analgesic activity. Homoveratryl substituted derivative was found to possess highest anti-inflammatory and analgesic activity displaying 73.60 % inhibition of edema at 40 mg/kg with no ulcerogenic activity when compared to standard drugs indomethacin. Moreover, 2-substituted-4-benzo[d][1,3]dioxole-6-phenylpyridazin-3(2H)-ones derivatives did not produce significant changes in bleeding time and emerged as safe agents. Molecular docking studies also illustrated good binding interactions at the active site of the cyclooxygenase-2 (hCox-2) enzyme.

Keywords: anti-inflammatory, analgesic, pyridazin-3(2H)-one, selective COX-2 inhibitors

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Authors: Surbhi Aggarwal, Jaishree Paul

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

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

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

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

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

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Authors: Helga Martins, Idália Matias

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Background:Multiple sclerosis is a chronic inflammatory autoimmune demyelinating disease that affects young adults. Multiple sclerosis is a chronic disease in which the patient needs to self-manage the disease and the therapeutic regimen. Consequently, the promotion of health literacy assumes a relevant role for the accessibility, understanding, and use of information in order to promote and maintain the health of patients with multiple sclerosis. Aim: To determine the impact of lower health literacy in the self-management of patients with a multiple sclerosis. Methods: Literature review based on a search on the following electronic databases: CINAHLand MEDLINE; comprising all results published between September 2016 and September 2021. The search strategy was: (“Self-management [MeSH]” AND “Multiple sclerosis[MeSH]”AND “Health literacy[MeSH]”). The inclusion criteria were: original papers reporting about multiple sclerosis patients; participants with age above 18 years old, written in English, Spanish, French, or Portuguese. Two independent reviewers have done the screening and analysis of the results. 38 citations were identified, and after duplicates removal, a total of 25 results were screened; 14 were included after the application of the inclusion criteria. Results: The lower health literacy in the self-management of patients with a multiple sclerosis is related toless healthy choices, riskier health behavior, poor health outcomes, decreased of adhering to the therapeutic regimen after discharge, less self-management of chronic illness, and increased the time of hospitalization. Conclusion: Inadequate levels of health literacy contribute to poor health outcomes, unsuccessful self-management of chronic illness, and inadequate adherence to the therapeutic regimen. Therefore, health literacy is important for health policy and the healthcare services, as it can be understood as a mediator of self-management of multiple sclerosis disease.

Keywords: health literacy, multiple sclerosis, review, self-management

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Authors: Sharareh Sharifi

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In this study, the crude extracts of Virgularia gustavina were examined as antibacterial, antifungal and anti-inflammatory agent. To assess inflammation, Xylene was applied to the ear of mice. The mice of the experimental group were fed with doses of 10 mg/kg, 20 mg/kg, and 40 mg/kg of lipid extract of chloroform and hexane as a separate group and then statistical analysis was performed on the results. Chloroform and hexane extracts of sea pen have strong anti-inflammatory effects even at low doses which is probably due to 54% arachidonic acid. Antibacterial and antifungal effects of hexane and chloroform extracts were measured with MIC and MBC methods and it is shown that chloroform extract has best activity against Staphylococcus aureus on 125 µg/ml doze in MIC method.

Keywords: sea pen (virgularia gustaviana), lipid extract, anti-inflammatory and anti-bacterial activities, fatty acid

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Authors: Beata Skibska, Andrzej Stanczak, Agnieszka Skibska

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Nanodiamond (ND) is a carbon nanomaterial that has high biocompatibility, and it has a very positive effect on a number of biochemical processes. NDs have great potential in treating multiple inflammation-associated diseases. The purpose of this study was to investigate the anti-inflammatory effect of nanodiamonds and lipoic acid (LA) (as antioxidants) on rats' cardiovascular systems after lipopolysaccharide (LPS) administration. Animal experiments enabled the determination of how nanodiamonds act when applied independently or in combination with lipoic acid. The effect of NDs and LA on C-reactive protein (CRP) levels and heart edema was evaluated. NDs and LA administered after LPS administration attenuated heart edema and significantly decreased the CRP level. The results suggest that NDs and LA play an important role in LPS-induced inflammation in the heart. NDs find new applications in modern biomedical science and biotechnologies.

Keywords: nanodiamonds, lipoic acid, inflammation, cardiovascular system

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Authors: Sani Ismaila, Shafiu Yau, Abubakar Salisu, Buhari Salisu, Sharifat Balogun, Mustapha Abubakar, Biobaku Khalid, Agaie Bello

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Over the years, Japanese quail egg has been in use in the management of diseases. The objective of this study was to evaluate the analgesic, anti-inflammatory and gastroprotective effects of raw Quail egg (yolk + albumin) in rats. Pain was assessed in rats by recording the latent period and writing reflex, anti-inflammatory effect was determined using both motility and compression test, while the gastro-protective effects were assessed by observing the histology of the stomach after diclofenac-induced gastric ulcers and subsequent treatment with the quail egg, Rats were randomly assigned into 4 groups; Groups I: were the control non-treated (NT), Group II were treated with Tramadol 50 mg/kg/Os (TMD) or Indomethacin (IND) 5mg/kg/Os (positive control for the writhing reflex determination), while group III and IV were treated with 3 and 6g/kg of raw quail egg respectively). Groups treated with quail egg in both doses showed a significant increase in the latent period (p <0 .05) when compared to the control NT, but lower than the group treated with tramadol at 20mins interval (p<0.05). Writing reflexes decrease in groups II, III, and IV compared to the NT group (p < 0.05). While motility increases significantly (p < 0.05) in groups II, compared to I (p<0.05). Control non-treated rats showed a quicker and extensive response to compression using the Vanier calliper on the inflamed paw compared to groups II-IV (p < 0.05). Histological studies of the stomach revealed sloughing of the epithelia, cellular infiltration with micro abscesses in the non-treated, while groups treated concurrently with quail egg showed proliferation of the glandular epithelia and goblet cells, and those treated 30 minutes before diclofenac administration showed proliferation of glands and thickening of the squamous epithelia. This study showed that quail egg has analgesic, anti-inflammatory and gastro-protective potentials and can be used as adjuvant treatment whenever COX-2 enzymes inhibitors are indicated.

Keywords: analgesia, anti-inflammatory, gastroprotective effect, japanese quail egg

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Authors: Watchareewan Thongsaard, Ratirat Sangpayap, Maneekarn Namsa-Aid

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Thunbergia laurifolia Linn. (TL) is a herbal medicine which has been used as an antidote for several poisonous agents including insecticides and as a component of a mixture of crude extracts to treat drug addicted patients. The aim of this study is to examine the level of dopamine in nucleus accumbens after chronic pre-administration of TL in ethanol addicted rats. Male Wistar rats weigh 200-250 g received TL methanol extract (200mg/kg, orally) 60 minutes before 20% ethanol (1 g/kg, i.p.) for 30 days. The nucleus accumbens was removed and tested for dopamine by HPLC-ECD. The level of dopamine was significantly increased by chronic ethanol administration, whereas the chronic TL extract administration did not cause a difference in dopamine level when compared to control. Moreover, the pre-treatment of TL extract before ethanol significantly reduced the dopamine level in nucleus accumbens to normal level when compared with chronic ethanol administration alone. These results suggested that the increase in dopamine level in the nucleus accumbens by chronic ethanol administration is the cause of ethanol addiction, and this effect is prevented by chronic TL pre-administration. Furthermore, chronic TL extract administration alone did not cause the changes in dopamine level in the nucleus accumbens, indicating that TL itself did not cause addiction.

Keywords: Thunbergia laurifolia Linn., alcohol addiction, dopamine, nucleus accumbens

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Authors: Yi-Feng Kao, Huey-Jine Chai, Chin-I Chang, Yi-Chen Chen, June-Ru Chen

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Microglia is a macrophage that resides in brain, and overactive microglia may result in brain neuron damage or inflammation. In this study, the phospholipids was extracted from squid skin and manufactured into a liposome (SQ liposome) to mimic apoptotic body. We then evaluated anti-inflammatory effects of SQ liposome on mouse microglial cell line (BV-2) by lipopolysaccharide (LPS) induction. First, the major phospholipid constituents in the squid skin extract were including 46.2% of phosphatidylcholine, 18.4% of phosphatidylethanolamine, 7.7% of phosphatidylserine, 3.5% of phosphatidylinositol, 4.9% of Lysophosphatidylcholine and 19.3% of other phospholipids by HPLC-UV analysis. The contents of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the squid skin extract were 11.8 and 28.7%, respectively. The microscopic images showed that microglia cells can engulf apoptotic cells or SQ-liposome. In cell based studies, there was no cytotoxicity to BV-2 as the concentration of SQ-liposome was less than 2.5 mg/mL. The LPS induced pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), were significant suppressed (P < 0.05) by pretreated 0.03~2.5mg/ml SQ liposome. Oppositely, the anti-inflammatory cytokines transforming growth factor-beta (TGF-β) and interleukin-10 (IL-10) secretion were enhanced (P < 0.05). The results suggested that SQ-liposome possess anti-inflammatory properties on BV-2 and may be a good strategy for against neuro-inflammatory disease.

Keywords: apoptotic mimicry, neuroinflammation, microglia, squid processing by-products

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Authors: Shao-Ju Chien, Yi-Chien Wu, Ting-Ying Huang, Li-Tsen Li, You-Jin Chen, Cheng-Nan Chen

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Homocysteine and pro-inflammatory mediators such as cyclooxygenase-2 (COX-2) have been linked to vascular dysfunction and risks of cardiovascular diseases. Fulvic acid (FA) is class of compounds of humic substances and possesses various pharmacological properties. However, the effect of FA on inflammatory responses of the monocytes remains unclear. We investigated the regulatory effect of FA on homocysteine-induced COX-2 expression in human monocytes. Peripheral blood monocytes and U937 cells were kept as controls or pre-treated with FA, and then stimulated with homocysteine. The results show that pretreating monocytes with FA inhibited the homocysteine-induced COX-2 expression in a dose-dependent manner. The inhibitor for nuclear factor-kB (NF-kB) attenuated homocysteine-induced COX-2 expression. Our findings provide a molecular mechanism by which FA inhibit homocysteine-induced COX-2 expression in monocytes, and a basis for using FA in pharmaceutical therapy against inflammation.

Keywords: homocysteine, monocytes, cyclooxygenase-2, fulvic acid, anti-inflammation

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Authors: Somaiya Mateen, Shagufta Moin, Abdul Qayyum, Atif Zafar

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Cytokines and reactive species play an important role in the pathophysiology of rheumatoid arthritis (RA). This study was done to determine the levels of reactive oxygen and nitrogen species (ROS and RNS), inflammatory cytokines and the markers of protein, DNA and lipid oxidation in the blood of RA patients, with the aim to study the antioxidant and anti-inflammatory role of moderate intensity exercises in the management of RA. RA patients were subdivided into two groups- first group (n=30) received treatment with conventional RA drugs while the second group (n=30) received moderate exercise therapy along with the conventional drugs for a period of 12 weeks. The levels of ROS, RNS, inflammatory cytokines and markers of biomolecule oxidation were monitored before and after 12 weeks of treatment. RA patients showed a marked increase in the levels of ROS, RNS, inflammatory cytokines, lipid, protein and DNA oxidation as compared to the healthy controls. These parameters were ameliorated after treatment with drugs alone and exercise combined with drugs, with the amelioration being more significant in patients given drugs along with the moderate intensity exercise treatment. In conclusion, the role of ROS, RNS and inflammatory cytokines in the pathogenesis of RA has been confirmed by this study. These may also serve as potential biomarker for assessing the disease severity. Finally, the addition of moderate intensity exercises in the management of RA may be of great value.

Keywords: rheumatoid arthritis, reactive oxygen species, inflammatory cytokines, moderate intensity exercises

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Authors: Kwok W. Mui, Ling T. Wong, Nai K. K. Fong

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Chronic obstructive pulmonary disease (COPD) is the fifth leading cause of death in Hong Kong. Investigators are eager to explore the environmental risk factors for COPD such as air pollution and occupational exposure. Through a cross-sectional survey, this study investigates the impact of air quality to the quality of life of patients with the COPD in terms of the scores of the (Chinese) chronic respiratory questionnaire (CCRQ) and the measurements of indoor air quality (IAQ) and Moser’s activities of daily living (ADL). Strong relationships between a number of indoor/outdoor environmental parameters were found and CRQ sub-scores for patients of COPD and thus indoor air pollutants must be monitored for future studies related to QOL for patients with COPD.

Keywords: chronic obstructive pulmonary disease (COPD), indoor air pollutants, quality of life, chronic respiratory questionnaire (CRQ)

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Authors: Tauseef Ahmad, Muhammad Ishaq, Mathew Eapen, Ahyoung Park, Sam Karpiniec, Vanni Caruso, Rajaraman Eri

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Fucoidans are complex, fucose-rich sulfated polymers discovered in brown seaweeds. Fucoidans are popular around the world, particularly in the nutraceutical and pharmaceutical industries, due to their promising medicinal properties. Fucoidans have been shown to have a variety of biological activities, including anti-inflammatory effects. They are known to inhibit inflammatory processes through a variety of mechanisms, including enzyme inhibition and selectin blockade. Inflammation is a part of the complicated biological response of living systems to damaging stimuli, and it plays a role in the pathogenesis of a variety of disorders, including arthritis, inflammatory bowel disease, cancer, and allergies. In the current investigation, various fucoidan extracts from Undaria pinnatifida, Fucus vesiculosus, Macrocystis pyrifera, Ascophyllum nodosum, and Laminaria japonica were assessed for inhibition of pro-inflammatory cytokine production (TNF-α, IL-1β, and IL-6) in LPS induced human macrophage cell line (THP-1) and human peripheral blood mononuclear cells (PBMCs). Furthermore, we also sought to catalogue these extracts based on their anti-inflammatory effects in the current in-vitro cell model. Materials and Methods: To assess the cytotoxicity of fucoidan extracts, MTT (3-[4,5-dimethylthiazol-2-yl]-2,5, -diphenyltetrazolium bromide) cell viability assay was performed. Furthermore, a dose-response for fucoidan extracts was performed in LPS induced THP-1 cells and PBMCs after pre-treatment for 24 hours, and levels of TNF-α, IL-1β, and IL-6 cytokines were measured using Enzyme-Linked Immunosorbent Assay (ELISA). Results: The MTT cell viability assay demonstrated that fucoidan extracts exhibited no evidence of cytotoxicity in THP-1 cells or PBMCs after 48 hours of incubation. The results of the sandwich ELISA revealed that all fucoidan extracts suppressed cytokine production in LPS-stimulated PBMCs and human THP-1 cells in a dose-dependent manner. Notably, at lower concentrations, the lower molecular fucoidan (5-30 kDa) extract from Macrocystis pyrifera was a highly efficient inhibitor of pro-inflammatory cytokines. Fucoidan extracts from all species including Undaria pinnatifida, Fucus vesiculosus, Macrocystis pyrifera, Ascophyllum nodosum, and Laminaria japonica exhibited significant anti-inflammatory effects. These findings on several fucoidan extracts provide insight into strategies for improving their efficacy against inflammation-related diseases. Conclusion: In the current research, we have successfully catalogued several fucoidan extracts based on their efficiency in LPS-induced macrophages and PBMCs in downregulating the key pro-inflammatory cytokines (TNF-, IL-1 and IL-6), which are prospective targets in human inflammatory illnesses. Further research would provide more information on the mechanism of action, allowing it to be tested for therapeutic purposes as an anti-inflammatory medication.

Keywords: fucoidan, PBMCs, THP-1, TNF-α, IL-1β, IL-6, inflammation

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