Search results for: kidney disease

Authors: Christy Rosaline, Rathankar Roa, Waheeta Hopper

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Persistence of tuberculosis, emergence of multidrug-resistance and extensively drug-resistant forms of the disease, has increased the interest in developing new antitubercular drugs. Developing inhibitors for 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase from Mycobacterium tuberculosis (MtbDAH7Ps), an enzyme involved in shikimate pathway, gives a selective target for antitubercular agents. MtbDAH7Ps was screened against ZINC database, and shortlisted compounds were subjected to induce fit docking. Prime/Molecular Mechanics Generalized Born Surface Area calculation was used to validate the binding energy of ligand-protein complex. Molecular Dynamics analysis for of the lead compounds–MtbDAH7Ps complexes showed that the backbone of MtbDAH7Ps in their complexes were stable. These results suggest that the shortlisted lead compounds ZINC04097114, ZINC15163225, ZINC16857013, ZINC06275603, and ZINC05331260 could be developed into novel drug leads to inhibit DAH7Ps in Mycobacterium tuberculosis.

Keywords: MtbDAH7Ps, Mycobacterium tuberculosis, HTVS, molecular dynamics

Procedia PDF Downloads 179

Authors: Michal Christina Steven, Mohd. Yusof Hj Ibrahim, Haryati Abdul Karim, Prabakaran Dhanaraj, Kelly Alexius Mansin

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After 27 years, Malaysia reported polio cases in 2019 involving the children of the undocumented migrants living in Sabah. These undocumented migrants present a significant challenge in achieving the elimination of vaccine-preventable diseases (VPD). Due to the recent polio outbreak among the undocumented migrant children in Sabah, an in-depth interview was conducted among the caregivers of undocumented migrant children to identify the barriers and drivers towards vaccinating their children. Financial barriers, legal citizenship status, language barrier, the COVID-19 pandemic, and physical barriers have been the barriers to access vaccination services by undocumented migrants. Five significant drivers for undocumented migrants to vaccinate their children are social influence, fear of disease, parental trust in healthcare providers, good support, and vaccine availability. Necessary action should be taken immediately to address the problems of vaccinating the children of undocumented migrants to prevent the re-emergence of VPD.

Keywords: Malaysia, polio, Sabah, undocumented migrants

Procedia PDF Downloads 159

Authors: Monica Puri Sikka, Subrato Ghosh Arunangshu Mukhopadhyay

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Appropriate compression bandaging is important for compression therapeutic medical diseases. The high compression approach employed for treating venous leg ulcers should be used correctly so that sufficient (but not excessive) pressure is applied. Bandages used to treat venous disease by compression should achieve and sustain effective levels and gradients of pressure and minimise the risk of pressure trauma. To maintain graduated compression on the limb the bandage needs to be applied at same tension for each layer from ankle to the knee. In this paper the geometry for various bandaging procedures is used to wrap each layer of bandage by marking the relaxed length of the bandage. The relaxed length is calculated depending on the stretch, average circumference of the limb on which it is to be applied and the bandaging technique to be used. This paper aims at developing a scientific approach while applying the bandage to reduce the inter operator variability in applying same tension on each successive layer of bandage.

Keywords: bandaging, compression, inter operator variability, graduated, relaxed length, stretch

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Authors: Zainal Abedin

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Introduction: Reproductive health is one of the major priorities of global health and is a fundamental and inalienable part of women’s health due to childbearing, and it is closely associated with nutritional status. Objective: This study was done to assess reproductive health behavior and nutritional status of reproductive-age ethnic women residing in plain land. Method: It was a cross-sectional study conducted among conveniently selected 120 reproductive-aged ethnic women at three Upazila of Rajshahi District. Nutritional status was determined by the WHO cut-off value of BMI for the Asian population. Results: About 88% of respondents noticed that they seek treatment in response to disease, and most of them seek treatment from the pharmacy attendant. Two-thirds of women used contraceptives, and 76% of women received antenatal care visits from Govt health centers, private clinics, and NGO clinics, but 86% of respondents delivered at home. In terms of nutritional status, 70% were normal, 23% underweight, and 7% overweight. Conclusion: Though most of them were normal regarding nutritional status but one-fourth were still underweight. Local pharmacy/quack-dependent treatment should be reduced.

Keywords: reproductive health behavior, nutritional status, plain land, ethnic women

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Authors: Jasminka Mujic, Karin Milde-Langosch, Volkmar Mueller, Mirza Suljagic, Tea Becirevic, Jozo Coric, Daria Ler

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MACC1 (metastasis associated in colon cancer-1) is a prognostic biomarker for tumor progression, metastasis, and survival of a variety of solid cancers. MACC1 also causes tumor growth in xenograft models and acts as a master regulator of the HGF/MET signaling pathway. In breast cancer, the expression of MACC1 determined by immunohistochemistry was significantly associated with positive lymph node status and advanced clinical stage. The aim of the present study was to further investigate the prognostic or predictive value of MACC1 expression in breast cancer using western blot analysis and immunohistochemistry. The results of our study have shown that high MACC1 expression in breast cancer is associated with shorter disease-free survival, especially in node-negative tumors. The MACC1 might be a suitable biomarker to select patients with a higher probability of recurrence which might benefit from adjuvant chemotherapy. Our results support a biologic role and potentially open the perspective for the use of MACC1 as predictive biomarker for treatment decision in breast cancer patients.

Keywords: breast cancer, biomarker, HGF/MET, MACC1

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Authors: P. J. Sweeney, T. Ahtoniemi, J. Puoliväli, T. Laitinen, K. Lehtimäki, A. Nurmi, D. Wells

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Duchenne muscular dystrophy (DMD) is caused by an X linked mutation in the dystrophin gene; lack of dystrophin causes a progressive muscle necrosis which leads to a progressive decrease in mobility in those suffering from the disease. The MDX mouse, a mutant mouse model which displays a frank dystrophinopathy, is currently widely employed in pre clinical efficacy models for treatments and therapies aimed at DMD. In general the end-points examined within this model have been based on invasive histopathology of muscles and serum biochemical measures like measurement of serum creatine kinase (sCK). It is established that a “critical period” between 4 and 6 weeks exists in the MDX mouse when there is extensive muscle damage that is largely sub clinical but evident with sCK measurements and histopathological staining. However, a full characterization of the MDX model remains largely incomplete especially with respect to the ability to aggravate of the muscle damage beyond the critical period. The purpose of this study was to attempt to aggravate the muscle damage in the MDX mouse and to create a wider, more readily translatable and discernible, therapeutic window for the testing of potential therapies for DMD. The study consisted of subjecting 15 male mutant MDX mice and 15 male wild-type mice to an intense chronic exercise regime that consisted of bi-weekly (two times per week) treadmill sessions over a 12 month period. Each session was 30 minutes in duration and the treadmill speed was gradually built up to 14m/min for the entire session. Baseline plasma creatine kinase (pCK), treadmill training performance and locomotor activity were measured after the “critical period” at around 10 weeks of age and again at 14 weeks of age, 6 months, 9 months and 12 months of age. In addition, kinematic gait analysis was employed using a novel analysis algorithm in order to compare changes in gait and fine motor skills in diseased exercised MDX mice compared to exercised wild type mice and non exercised MDX mice. In addition, a morphological and metabolic profile (including lipid profile), from the muscles most severely affected, the gastrocnemius muscle and the tibialis anterior muscle, was also measured at the same time intervals. Results indicate that by aggravating or exacerbating the underlying muscle damage in the MDX mouse by exercise a more pronounced and severe phenotype in comes to light and this can be picked up earlier by kinematic gait analysis. A reduction in mobility as measured by open field is not apparent at younger ages nor during the critical period, but changes in gait are apparent in the mutant MDX mice. These gait changes coincide with pronounced morphological and metabolic changes by non-invasive anatomical MRI and proton spectroscopy (1H-MRS) we have reported elsewhere. Evidence of a progressive asymmetric pathology in imaging parameters as well as in the kinematic gait analysis was found. Taken together, the data show that chronic exercise regime exacerbates the muscle damage beyond the critical period and the ability to measure through non-invasive means are important factors to consider when performing preclinical efficacy studies in the MDX mouse.

Keywords: Gait, muscular dystrophy, Kinematic analysis, neuromuscular disease

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Authors: Sadia Arshad

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The new coronavirus disease or COVID-19 still poses an alarming situation around the world. Modeling based on the derivative of fractional order is relatively important to capture real-world problems and to analyze the realistic situation of the proposed model. Weproposed a mathematical model for the investigation of COVID-19 dynamics in a generalized fractional framework. The new model is formulated in the Caputo sense and employs a nonlinear time-varying transmission rate. The existence and uniqueness solutions of the fractional order derivative have been studied using the fixed-point theory. The associated dynamical behaviors are discussed in terms of equilibrium, stability, and basic reproduction number. For the purpose of numerical implementation, an effcient approximation scheme is also employed to solve the fractional COVID-19 model. Numerical simulations are reported for various fractional orders, and simulation results are compared with a real case of COVID-19 pandemic. According to the comparative results with real data, we find the best value of fractional orderand justify the use of the fractional concept in the mathematical modelling, for the new fractional modelsimulates the reality more accurately than the other classical frameworks.

Keywords: fractional calculus, modeling, stability, numerical solution

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Authors: Avijit Dey, Antony Gomes, Subir Chandra Dasgupta

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Tea (Camellia sinensis) is the most popular beverages in the world and is ranked second after the water. Tea has been considered as a health promoting beverage since ancient times due to its health-promoting activity. Recently, immunomodulatory, anti-arthritic, antioxidant, anticancer and cardioprotective activity of tea has been established. Very few studies have demonstrated the effect of high dose of black tea on health. The aim of the present study was to evaluate the role of low & high dose of Black Tea Extract (BTE) on the different physiological parameters of mother and pups during prenatal and postnatal developmental period in the experimental rodent. BTE was orally administered in LD (50mg BTE/kg/day) and HD (100mg BTE/kg/day) except control groups of rats (n=6/group) throughout the prenatal (day 0-21) and postnatal (day 21-42) periods. During prenatal period (0, 7th, 14th, 20th days) body weight, urinary calcium, magnesium, urea and creatinine was measured. In postnatal period physical (0, 10th, 21th days) parameters of pups like body weight, cranial length, cranial diameter, neck width, tail length, craniosacral length of pups were analyzed. Liver and lungs from pups and kidney spleen, etc. from mothers were collected on day 42 for histopathological studies. The comparative urine strip and morphology of RBC was also analyzed by SEM from mothers of different groups on day 42. The level of cytokines like IL-1alpha, IL-1beta, IL-6, IL-10, TNF-alpha were analysed by enzyme-linked immunosorbent assay (ELISA) on day 0, day 20 and day 42. The body weight of LD and HD mothers were also significantly (P<0.05) less than control mothers at 20th day of pregnancy and there was also significant changes in urinary calcium, urea, creatinine. The bio morphometric analysis of pups showed significant alteration (P<0.05) in HD groups relative to control. Some histological alterations were also observed in pups and mothers. Comparative urine strip analysis and morphology of RBC showed significant changes in treated groups. LD and HD treated mothers showed an increase in proinflammatory cytokines like IL-1beta, TNF-alpha and decrease in anti-inflammatory cytokine-like IL-10 on day 20 compared to PC mothers. This study clearly indicated that high dose of BTE possesses detrimental effect on pregnant mother and the pup. Further studies are in progress to elucidate the molecular mechanism of actions. This project work has been sponsored by National Tea Research Foundation vide Project Sanction No.: 17 (305)/2013/4423 dated 11th March, 2014. All experimental protocols described in the study were approved by animal ethics committee.

Keywords: black tea extract, pregnancy, prenatal and postnatal development, inflammation

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Authors: Saira Baloch, Mohsin Ali Baloch

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Background: Malaria is a potentially life-threatening disease and also a major public health problem in Pakistan. Renal failure is an emerging problem correlated with morbidity and mortality, however can be diagnosed and treated in the early stages. Objectives: To elucidate the biochemical renal parameters in patients with falciparum malaria and comparison with healthy control subjects. Method: 80 patients, who were diagnosed to be affected by falciparum malaria. Detailed history, general physical and systemic examination and necessary pathological, biochemical renal laboratory parameters and investigations were done. Results: Among the 80 patients, 43 were males and 37 were females. All patients were infected with P. falciparum. All patients had increased serum creatinine and urea levels and urine output of less than 400 ml/day were categorized as suffering from renal failure. Conclusion: Patients infected with P. falciparum are at an increased risk of developing renal failure when compared to patients infected with other complications. P. vivax has massive potential to cause life threatening complications and even death. Further research is required to understand the exact pathogenesis of various complications encountered in vivax malaria.

Keywords: falciparum malaria, renal failure, biochemical parameters, pathogenesis

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Authors: Meiyan Xing, Cenran Li, Liang Xiang

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Impacts of excess sludge vermicompost on the germination and early growth of plant were tested. The better effect of cow dung vermicompost (CV) on seed germination and seedling growth proved that cow dung was indeed the preferred additive in sludge vermicomposting as reported by plentiful researchers worldwide. The effects and the best amount of application of CV were further discussed. Results demonstrated that seed germination and seedling growth (seedlings number, plant height, stem diameter) were the best and heavy metal (Zn, Pb, Cr and As) contents of plant were the lowest when soil amended with CV by 15%. Additionally, CV fostered higher contents of chlorophyll a and chlorophyll b compared to the control when concentration ranged from 5 to 15%, thereafter a slight increase in chlorophyll content was observed form 15% to 25%. Thus, CV at the optimum proportion of 15% could serve as a feasible and satisfactory way of sludge agricultural utilization of sewage sludge. In summary, sewage sludge can be gainfully utilized in producing organic fertilizer via vermicomposting, thereby not only providing a means of sewage sludge treatment and disposal, but also stimulating the growth of plant and the ability to resist disease.

Keywords: cow dung vermicompost, seed germination, seedling growth, sludge utilization

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Authors: Kaustubh Chakradeo, Michael Delves, Sofya Titarenko

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Malaria is a serious disease which affects hundreds of millions of people around the world, each year. If not treated in time, it can be fatal. Despite recent developments in malaria diagnostics, the microscopy method to detect malaria remains the most common. Unfortunately, the accuracy of microscopic diagnostics is dependent on the skill of the microscopist and limits the throughput of malaria diagnosis. With the development of Artificial Intelligence tools and Deep Learning techniques in particular, it is possible to lower the cost, while achieving an overall higher accuracy. In this paper, we present a VGG-based model and compare it with previously developed models for identifying infected cells. Our model surpasses most previously developed models in a range of the accuracy metrics. The model has an advantage of being constructed from a relatively small number of layers. This reduces the computer resources and computational time. Moreover, we test our model on two types of datasets and argue that the currently developed deep-learning-based methods cannot efficiently distinguish between infected and contaminated cells. A more precise study of suspicious regions is required.

Keywords: convolution neural network, deep learning, malaria, thin blood smears

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Authors: Pedro Felgueiras, Ana Miguel, Nélson Almeida, Raquel Silva

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Objective: Through the study of a clinical case of delusional somatic disorder secondary to phantogeusia, we aim to highlight the importance of considering psychosomatic conditions in differential diagnosis, as well as to emphasize the complexity of its comprehension, treatment, and respective impact on patients’ functioning. Methods: Bearing this in mind, we conducted a critical analysis of a case series based on patient observations, clinical data, and complementary diagnostic methods, as well as a non-systematic review of the literature on the subject. Results: A 61-year-old female patient with no history of psychiatric conditions. Family psychiatric history of mood disorder (depression), with psychotic features found in her mother. Medical history of many comorbidities affecting different organ systems (endocrine, gastrointestinal, genitourinary, ophthalmological). Documented neuroticism traits of personality. The patient’s family described a persistent concern about several physical symptoms across her life, with a continuous effort to obtain explanations about any sensation out of her normal perception. Since being subjected to endoscopy in 2018, she started complaints of persistent phantogeusia (acid taste) and developed excessive thoughts, feelings, and behaviors associated with this somatic symptom. The patient was evaluated by several medical specialties, and an extensive panel of medical exams was carried out, excluding any disease. Besides all the investigation and with no evidence of disease signs, acute anxiety, time, and energy dispended to this symptom culminated in severe psychosocial impairment. The patient was admitted to a psychiatric ward for investigation and treatment of this clinical picture, leading to the diagnosis of the delusional somatic disorder. In order to exclude the acute organic etiology of this psychotic disorder, an analytic panel was carried out with no abnormal results. In the context of a psychotic clinical picture, a CT scan was performed, which revealed a right cortical vascular lesion. Neuropsychological evaluation was made, with the description of cognitive functioning being globally normative. During treatment with an antipsychotic (pimozide), a complete remission of the somatic delusion was associated with the disappearance of gustative perception disturbance. In follow-up, a relapse of gustative sensation was documented, and her thoughts and speech were dominated by concerns about multiple somatic symptoms. Conclusion: In terms of abnormal bodily sensations, the oral cavity is one of the frequent sites of delusional disorder. Patients with these gustatory perception distortions complain about unusual sensations without corresponding abnormal findings in the oral area. Its pathophysiology has not been fully elucidated yet. In terms of its comprehensive psychopathology, this case was hypothesized as a paranoid development of a delusional somatic disorder triggered by a post-invasive procedure phantogeusia (which is described as a possible side effect of an endoscopy) in a patient with an anankastic personality. This case presents interesting psychopathology, reinforcing the complexity of psychosomatic disorders in terms of their etiopathogenesis, clinical treatment, and long-term prognosis.

Keywords: psychosomatics, delusional somatic disorder, phantogeusia, paranoid development

Procedia PDF Downloads 129

Authors: Felix Lankester, Alicia Davis, Safari Kinung'hi, Catherine Bunga, Shayo Alkara, Imam Mzimbiri, Jonathan Yoder, Sarah Cleaveland, Guy H. Palmer

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Achieving the London Declaration goal of a 90% reduction in neglected tropical diseases (NTDs) by 2030 requires cost-effective strategies that attain high and comprehensive coverage. The first objective of this trial was to assess the impact on cost and coverage of employing a novel integrative One Health approach linking two NTD control programs: mass drug administration (MDA) for soil-transmitted helminths in humans (STH) and mass dog rabies vaccination (MDRV). The second objective was to compare the coverage achieved by the MDA, a community-wide deworming intervention, with that of the existing national primary school-based deworming program (NSDP), with particular focus on the proportion of primary school-age children reached and their school enrolment status. Our approach was unconventional because, in line with the One Health approach to disease control, it coupled the responsibilities and resources of the Ministries responsible for human and animal health into one program with the shared aim of preventing multiple NTDs. The trial was carried out in hard-to-reach pastoral communities comprising 24 villages of the Ngorongoro District, Tanzania, randomly allocated to either Arm A (MDA and MDRV), Arm B (MDA only) or Arm C (MDRV only). Objective one: The percentage of people in each target village that received treatment through MDA in Arms A and B was 63% and 65%, respectively (χ2 = 1, p = 0.32). The percentage of dogs vaccinated in Arm A and C was 70% and 81%, respectively (χ2 =9, p = 0.003). It took 33% less time for a single person and a dog to attend the integrated delivery than two separate events. Cost per dose (including delivery) was lower under the integrated strategy, with delivery of deworming and rabies vaccination reduced by $0.13 (54%) and $0.85 (19%) per dose, respectively. Despite a slight reduction in the proportion of village dogs vaccinated in the integrated event, both the integrated and non-integrated strategies achieved the target threshold of 70% required to eliminate rabies. Objective two: The percentages of primary school age children enrolled in school that was reached by this trial (73%) and the existing NSDP (80%) were not significantly different (F = 0.9, p = 0.36). However, of the primary school age children treated in this trial, 46% were not enrolled in school. Furthermore, 86% of the people treated would have been outside the reach of the NSDP because they were not primary school age or were primary school age children not enrolled in school. The comparable reach, the substantial reductions in cost per dose delivered and the decrease in participants’ time support this integrated One Health approach to control multiple NTDs. Further, the recorded level of non-enrolment at primary school suggests that, in remote areas, school-based delivery strategies could miss a large fraction of school-age children and that programs that focus delivery solely at the level of the primary school will miss a substantial proportion of both primary school age children as well as other individuals from the community. We have shown that these populations can be effectively reached through extramural programs.

Keywords: canine mediated human rabies, integrated health interventions, mass drug administration, neglected tropical disease, One Health, soil-transmitted helminths

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Authors: Walid Mousa, Mohamed Nayel, Ahmed Zaghawa, Akram Salama, Ahmed El-Sify, Hesham Rashad, Dina El-Shafey

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Mycoplasmosis in small ruminants constitutes a serious contagious problem in smallholders causing severe economic losses worldwide. This study was conducted to determine the clinical, Minimum Inhibitory Concentration (MIC) and molecular characterization of Mycoplasma species associated in sheep breeding herds in Menoufiya governorate, Egypt. Out of the examination of 400 sheep, 104 (26%) showed respiratory manifestations, nasal discharges, cough and conjunctivitis with systemic body reaction. Meanwhile, out of these examined sheep, only 56 (14%) were positive for mycoplasma isolation onto PPLO(Pleuropneumonia-like organisms) specific medium. The MIC for evaluating the efficacy of sensitivity of Mycoplasma isolates against different antibiotics groups revealed that both the Linospectin and Tylosin with 2ug, 0.25ug/ml concentration were the most effective antibiotics for Mycoplasma isolates. The application of PCR was the rapid, specific and sensitive molecular approach for detection of M. ovipneumoniae, and M. arginine at 390 and 326 bp, respectively, in all tested isolates. In conclusion, the diagnosis of Mycoplsamosis in sheep is important to achieve effective control measures and minimizing the disease dissemination among sheep herds.

Keywords: MIC, mycoplasmosis, PCR, sheep

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Authors: Kwanchai Ratanamanee, Pattra Ahmadi Pirshahid, Yaowaluk Khamphan, Sirinan Thubthimthad

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Obesity is a main global health problem. The obesity rated has continued to be higher and higher. It causes to serious systems, diabetes, coronary artery disease, stroke, and some types of cancer. Oristat is one of the best drugs worldwide used as a pancreatic lipase inhibitor. To develop the new therapeutic drugs from medicinal plant always explored. In this study, 24 medicinal plants were investigated for their pancreatic lipase and cholesterol esterase inhibitory effects with Fluorometer assay and oristat as a positive control. It showed that the ethanolic extract of pods of Acacia concinna (Willd.) D.C., possess pancreatic lipase and cholesterol esterase inhibitory activities of IC50 at 2.73 and 3.77 mg/ml respectively as well as oral acute toxicity of the extract (LD50) was 6,300 mg/kg body weight. The extract of A.concinna should be further investigated in animal testing. The results of pancreatic lipase and cholesterol esterase inhibitor of the extracts will lead us to utilize A.concinna for developing as obesity dietary supplement from a medicinal plant.

Keywords: Acacia concinna (Willd.) D. C., cholesterol esterase, obesity, pancreatic lipase

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Authors: Samineh Barmaki, Ville Jokinen, Esko Kankuri

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We report a microfluidic chip that can be used to modify the gaseous microenvironment of a cell-culture in ambient atmospheric conditions. The aim of the study is to show the cellular response to nitric oxide (NO) under hypoxic (oxygen < 5%) condition. Simultaneously targeting to hypoxic and nitric oxide will provide an opportunity for NO‑based therapeutics. Studies on cellular responses to lowered oxygen concentration or to gaseous mediators are usually carried out under a specific macro environment, such as hypoxia chambers, or with specific NO donor molecules that may have additional toxic effects. In our study, the chip consists of a microfluidic layer and a cell culture well, separated by a thin gas permeable polydimethylsiloxane (PDMS) membrane. The main design goal is to separate the gas oxygen scavenger and NO donor solutions, which are often toxic, from the cell media. Two different types of gas exchangers, titled 'pool' and 'meander' were tested. We find that the pool design allows us to reach a higher level of oxygen depletion than meander (24.32 ± 19.82 %vs -3.21 ± 8.81). Our microchip design can make the cells culture more simple and makes it easy to adapt existing cell culture protocols. Our first application is utilizing the chip to create hypoxic conditions on targeted areas of cell culture. In this study, oxygen scavenger sodium sulfite generates hypoxia and its effect on human embryonic kidney cells (HEK-293). The PDMS membrane was coated with fibronectin before initiating cell cultures, and the cells were grown for 48h on the chips before initiating the gas control experiments. The hypoxia experiments were performed by pumping of O₂-depleted H₂O into the microfluidic channel with a flow-rate of 0.5 ml/h. Image-iT® reagent as an oxygen level responser was mixed with HEK-293 cells. The fluorescent signal appears on cells stained with Image-iT® hypoxia reagent (after 6h of pumping oxygen-depleted H₂O through the microfluidic channel in pool area). The exposure to different levels of O₂ can be controlled by varying the thickness of the PDMS membrane. Recently, we improved the design of the microfluidic chip, which can control the microenvironment of two different gases at the same time. The hypoxic response was also improved from the new design of microchip. The cells were grown on the thin PDMS membrane for 30 hours, and with a flowrate of 0.1 ml/h; the oxygen scavenger was pumped into the microfluidic channel. We also show that by pumping sodium nitroprusside (SNP) as a nitric oxide donor activated under light and can generate nitric oxide on top of PDMS membrane. We are aiming to show cellular microenvironment response of HEK-293 cells to both nitric oxide (by pumping SNP) and hypoxia (by pumping oxygen scavenger solution) in separated channels in one microfluidic chip.

Keywords: hypoxia, nitric oxide, microenvironment, microfluidic chip, sodium nitroprusside, SNP

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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: Laila Montaser, Hala Gabr, Maha El-Bassuony, Gehan Tawfeek

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Orthotropic liver transplantation (OLT) is the final procedure of both end stage and metabolic liver diseases. Hepatocyte transplantation is an alternative for OLT, but the sources of hepatocytes are limited. Bone marrow mesenchymal stem cells (BM-MSCs) can differentiate into hepatocyte-like cells and are a potential alternative source for hepatocytes. The MSCs from bone marrow are a promising target population as they are capable of differentiating along multiple lineages and, at least in vitro, have significant expansion capability. MSCs from bone marrow may have the potential to differentiate in vitro and in vivo into hepatocytes. Our study examined whether mesenchymal stem cells (MSCs), which are stem cells originated from human bone marrow, are able to differentiate into functional hepatocyte-like cells in vitro. Our aim was to investigate the differentiation potential of BM-MSCs into hepatocyte-like cells. Adult stem cell therapy could solve the problem of degenerative disorders, including liver disease.

Keywords: bone marrow, differentiation, hepatocyte, stem cells

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Authors: Iqbal Ahmed Chowdhury

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Diarrhea is considered to be one of the influential factors of child death in Bangladesh. While it is known that diarrhea is a water-driven disease, due to the lack of studies, little is known about the extent to which various feeding patterns contribute to such an incidence. Our paper intends to fill this gap by looking into different feeding patterns and their influence on diarrhea incidence among children in Bangladesh. Using data collected for the Demographic and Health Survey, 2014, this paper reveals that feeding patterns can influence the diarrhea incidence among this group of children to a great extent. This paper finds that the incidence of diarrhea is likely to elevate if diarrhea-affected children are fed plain water from any source and any kind of juice. However, breastfeeding, feeding soup or clear broth, prescribed baby food, and clean water from a tube well tend to help fight diarrhea incidence among children in Bangladesh. The results are found to be consistent even after controlling for sociodemographic variables, including age and sex of children, age and education qualification of the parent, and the number of children in the family. The results of this study could contribute to treating diarrhea among children in Bangladesh as well as similar other countries in the world.

Keywords: feeding patterns, diarrhea, Bangladesh, children

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Authors: Mahesh Pal, Tripti Mishra, Chandana Rao, Dalip Upreti

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Cancer has been considered to be a very dreadful disease. Holmskioldia sanguinea is a large climbing shrub found in the Himalayas at an altitude of 5,000 ft and preliminary investigation showed the excellent yield of andrographolide and subjected for the anticancer activity. Protective effect of Holmskioldia sanguinea leaf ethanolic extract has been investigated against Ehrlich ascites carcinoma (EAC) and Daltons ascites lymphoma (DAL) in Swiss albino mice to evaluate the possible mechanism of action. The enzymatic antioxidant status was studied on tumor bearing mice, which shows the potential of the compound to possess significant free radical scavenging property and revealed significant tumor regression and prolonged survival time. The isolated bioactive molecule andrographolide from Holmskioldia sanguinea yields (2.5%) in subject to HPTLC/HPLC analysis. The cellular defense system constituting the superoxide dismutase, catalyses was enhanced whereby the lipid peroxidation content was restricted to a larger extent. The Holmskioldia sanguinea is a new source of andrographolide and demonstrated the potency in treatment of cancer.

Keywords: Holmskioldia sanguinea, tumor, mice, andrographolide

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Authors: Boxiang Zhuang

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This study analyzes the clinical manifestations, hearing rehabilitation methods and outcomes of a complex case of neurofibromatosis type II (NF2). Methods: The clinical manifestations, medical history, clinical data, surgical methods and postoperative hearing rehabilitation outcomes of an NF2 patient were analyzed to determine the hearing reconstruction method and postoperative effect for a special type of NF2 acoustic neuroma. Results: The patient had bilateral acoustic neuromas with profound sensorineural hearing loss in both ears. Peripheral blood genetic testing did not reveal pathogenic gene mutations, suggesting mosaicism. The patient had an intracochlear schwannoma in the right ear and severely impaired vision in both eyes. Cochlear implantation with tumor retention was performed in the right ear. After 2 months of family-based auditory and speech rehabilitation, the Categories of Auditory Performance (CAP) score improved from 0 to 5. Conclusion: NF2 has complex clinical manifestations and poor prognosis. For NF2 patients with intracochlear tumors, cochlear implantation with tumor retention can be used to reconstruct hearing.

Keywords: NF2, intracochlear schwannoma, hearing reconstruction, cochlear implantation

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Authors: R. S. Mehta, G. N. Mandal

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Hepatitis-B is the major infectious disease of mankind. In Nepal it is reported that more than 4.3% of Nepalese population at any time in their life has been infected with Hepatitis-B virus (HBV). The objective of this study was to evaluate the effectiveness of planned educational programme regarding knowledge and practice of hepatitis-B among the nurses working at medical units of BPKIHS. Pre-experimental research design was used to conduct the study among the nurses working in medical units of BPKIHS. Total 40 nurses were included in the pre-test and 34 in the post-test. The education intervention was arranged on 24th May 2012 from 2:15 pm to 4:45 pm i.e. two and half hours. After two weeks of education intervention post-test was conducted. Most of the participants (60%) were of the age group of 18-22 years, Hindu (82.5%), and unmarried (65%). After education intervention there is significant differences in knowledge on the components of Hepatitis-B at 0.05 level of significance. There is no difference in the attitude components after post-test except the component patient contaminated with Hepatitis-B must be called as the last patient (p=0.035). It can conclude that hepatitis-B educational program improved knowledge and practice among the nurses.

Keywords: educational program, Hepatitis-B, pre-experimental design, medical units

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Authors: Bailey Hall, Athena Hoppe, Tevyn Kagele, Anna Nichols, Breeanna Messner

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The Spokane Street Medicine (SSM) Program aims to deliver medical care to people experiencing homelessness in Spokane, Washington. Street medicine is designed to function in a non-traditional setting to help deliver healthcare to a largely underserved population. In this analysis, the SSM Program’s medical charts from street and shelter encounters in early 2021 were reviewed in order to identify illness and diseases in people experiencing homelessness in Spokane. More than half of the prescriptions written during these encounters were for either an antibacterial, an antibiotic, or an antifungal. Estimates of the cost to the local healthcare system are included. Initiating treatment for communicable diseases in people experiencing homelessness via street medicine efforts greatly reduces economic costs while improving health outcomes.

Keywords: ethical issues in public health, equity issues in public health, health economics, health disparities, healthcare costs, medical public health, public health ethics, street medicine

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Authors: Qingxin Chen, Liben Jiang, Andrew Smith, Karim Hadjri

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Since 2007, the Chinese food industry has undergone serious food contamination in the baby dairy industry, especially milk powder contamination. One of the milk powder products was found to contain melamine and a significant number (294,000) of babies were affected by kidney stones. Due to growing concerns among consumers about food safety and protection, and high pressure from central government, companies must take radical action to ensure food quality protection through the use of an appropriate quality management system. Previously, though researchers have investigated the health and safety aspects of food industries and products, quality issues concerning food products in China have been largely over-looked. Issues associated with baby dairy products and their quality issues have not been discussed in depth. This paper investigates the impact of quality management systems on the Chinese baby dairy product industry. A literature review was carried out to analyse the use of quality management systems within the Chinese milk power market. Moreover, quality concepts, relevant standards, laws, regulations and special issues (such as Melamine, Flavacin M1 contamination) have been analysed in detail. A qualitative research approach is employed, whereby preliminary analysis was conducted by interview, and data analysis based on interview responses from four selected Chinese baby dairy product companies was carried out. Through the analysis of literature review and data findings, it has been revealed that for quality management system that has been designed by many practitioners, many theories, models, conceptualisation, and systems are present. These standards and procedures should be followed in order to provide quality products to consumers, but the implementation is lacking in the Chinese baby dairy industry. Quality management systems have been applied by the selected companies but the implementation still needs improvement. For instance, the companies have to take measures to improve their processes and procedures with relevant standards. The government need to make more interventions and take a greater supervisory role in the production process. In general, this research presents implications for the regulatory bodies, Chinese Government and dairy food companies. There are food safety laws prevalent in China but they have not been widely practiced by companies. Regulatory bodies must take a greater role in ensuring compliance with laws and regulations. The Chinese government must also play a special role in urging companies to implement relevant quality control processes. The baby dairy companies not only have to accept the interventions from the regulatory bodies and government, they also need to ensure that production, storage, distribution and other processes will follow the relevant rules and standards.

Keywords: baby dairy product, food quality, milk powder contamination, quality management system

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Authors: Mohammad Reza Mohammadi, Layegheh Daliri

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Introduction: Leishmaniasis occurs in infectious diseases of Leishmania protozoa in Afghanistan, anthroponotic leishmaniasis and common cutaneous leishmaniasis (ZCL). Anthroponotic skin leishmania tropica may cause urban diseases and transmitted by Phlebotomus Sergenti. In different parts of Afghanistan, different species of Leishmania are observed. We report the epidemiological characteristics of prevention and treatment in this study. Methods: This study examines the epidemiology and prevention of religious diseases in Afghanistan. Knowledge gaps were analyzed and collected with our own data. Results: In Afghanistan, most of the Lishmania Tropic seekers are Four species of Leishmania in northern Afghanistan, including Leishmania Tropica, L. Major and L. Donovani, cause skin lesions, but L. Donovani and L. infantum are visible. Even combined prevention can significantly reduce the amount of infection. Conclusion: Skinny, as well as visceral leishmaniasis, can occur among the returnees from Afghanistan. Unusual and poor skin lesions can be created by L. Donovani. In most pathogenic areas, the transmission of common diseases between humans and animals. Home dogs are the main reservoir, transferring in some areas such as India and Sudan.

Keywords: leishmania donovani, leishmania tropica, treatment, disease, epidemiology

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Authors: Doni Dermawan

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Hypertension is a disease with a high prevalence in Indonesia. The prevalence of hypertension in Indonesia is based on the Basic Health Research (Riskesdas) in 2013 which amounted to 25.8%. Medicinal plants have been widely used to treat hypertension including roselle (Hibiscus sabdariffa L.) and garlic (Allium sativum L.) by a mechanism as angiotensin converting enzyme (ACE) inhibitor. The purpose of this research is to analyze the in silico (molecular studies) of pharmacological effects and toxicity of roselle (Hibiscus sabdariffa L.) and garlic (Allium sativum L.) as well as a combination of both are used as antihypertensive herbs. The results of study showed that roselle (Hibiscus sabdariffa L.) and garlic (Allium sativum L.) have great potential as antihypertensive herbs based on the affinity and stability of active substances to specific receptor with a much better value than a of antihypertensive drugs (lisinopril). Toxicity values determined by the method of AST, ALT and ALP in which the three values obtained indicate the presence of acute toxic effects that need to be considered in determining the dose of the extract of roselle and garlic as antihypertensives.

Keywords: Allium sativum, antihypertensive, Hibiscus sabdariffa, in silico, toxicity

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Authors: Taher Eid Shaaban Ahmed Mousa

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Non-Alcoholic fatty liver disease (NAFLD) is a major cause of multiple liver disorders, which strongly linked to a poor lifestyle. This study aiming to elucidate the exercise program’s effectiveness on hepatic fat mobilization among nonalcoholic fatty liver patients. Subjects: A purposive sample of 150 adult male & female patients. Setting: National institute of liver out patient's clinics of Menoufia University. Tools: three tools I: An interviewing structured questionnaire, II: International Physical Activity Questionnaire, III: compliance assessment sheet. Results: There was statistically significant difference pre and post exercise program regarding total body weight, physical activity level and compliance that prevent new fat development with resolution of existing one. Conclusion: regular exercise is the best implemented approach as an initial step for the prevention, treatment and management of NAFLD. Recommendation: It is highly important to unravel the mechanism and dose by which each exercise specifically resolve various stages of liver diseases.

Keywords: exercise program, hebatic fat mobilization, nonalcoholic fatty liver patients, sport science

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Authors: Ekaterina Zvorykina

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Nowadays, Arctic and Antarctic regions are distinguished to be one of the most important strategic resources for global development. Nonetheless, living conditions in Arctic regions still demand certain improvements. As soon as the region is rarely populated, one of the main points of interest is health accommodation of the people, who migrate to Arctic region for permanent and shift work. At Arctic and Antarctic latitudes, personnel face polar day and polar night conditions during the time of the year. It means that they are deprived of natural sunlight in winter season and have continuous daylight in summer. Firstly, the change in light intensity during 24-hours period due to migration affects circadian rhythms. Moreover, the controlled artificial light in winter is also an issue. The results of the recent studies on night shift medical professionals, who were exposed to permanent artificial light, have already demonstrated higher risks in cancer, depression, Alzheimer disease. Moreover, people exposed to frequent time zones change are also subjected to higher risks of heart attack and cancer. Thus, our main goals are to understand how high latitude work and living conditions can affect human health and how it can be prevented. In our study, we analyze molecular and cellular factors, which play important role in circadian rhythm change and distinguish main risk groups in people, migrating to high latitudes. The main well-studied index of circadian timing is melatonin or its metabolite 6-sulfatoxymelatonin. In low light intensity melatonin synthesis is disturbed and as a result human organism requires more time for sleep, which is still disregarded when it comes to working time organization. Lack of melatonin also causes shortage in serotonin production, which leads to higher depression risk. Melatonin is also known to inhibit oncogenes and increase apoptosis level in cells, the main factors for tumor growth, as well as circadian clock genes (for example Per2). Thus, people who work in high latitudes can be distinguished as a risk group for cancer diseases and demand more attention. Clock/Clock genes, known to be one of the main circadian clock regulators, decrease sensitivity of hypothalamus to estrogen and decrease glucose sensibility, which leads to premature aging and oestrous cycle disruption. Permanent light exposure also leads to accumulation superoxide dismutase and oxidative stress, which is one of the main factors for early dementia and Alzheimer disease. We propose a new screening system adjusted for people, migrating from middle to high latitudes and accommodation therapy. Screening is focused on melatonin and estrogen levels, sleep deprivation and neural disorders, depression level, cancer risks and heart and vascular disorders. Accommodation therapy includes different types artificial light exposure, additional melatonin and neuroprotectors. Preventive procedures can lead to increase of migration intensity to high latitudes and, as a result, the prosperity of Arctic region.

Keywords: circadian rhythm, high latitudes, melatonin, neuroprotectors

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Authors: Zakir Hossain, Md. Saddam Hossain

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A nutritionally balanced diet and selection of appropriate species are important criteria in aquaculture. The present study was conducted to evaluate the effects of polyunsaturated fatty acids (PUFAs) and beta glucan containing diet on growth performance, feed utilization, maturation, immunity, early embryonic and larval development of endangered Pabdah catfish, Ompok pabda. In this study, squid extracted lipids and mushroom powder were used as the source of PUFAs and beta glucan, respectively, and formulated two isonitrogenous diets such as basal or control (CON) diet and treated (PBG) diet with maintaining 30% protein levels. During the study period, similar physicochemical conditions of water such as temperature, pH, and dissolved oxygen (DO) were 26.5±2 °C, 7.4±0.2, and 6.7±0.5 ppm, respectively in each cistern. The results showed that final mean body weight, final mean length gain, food conversion ratio (FCR), specific growth rate (SGR), food conversion efficiency (%), hepatosomatic index (HSI), kidney index (KI), and viscerosomatic index (VSI) were significantly (P<0.01 and P<0.05) higher in fish fed the PBG diet than that of fish fed the CON diet. The length-weight relationship and relative condition factor (K) of O. pabda were significantly (P<0.05) affected by the PBG diet. The gonadosomatic index (GSI), sperm viability, blood serum calcium ion concentrations (Ca²⁺), and vitellogenin level were significantly (P<0.05) higher in fish fed the PBG diet than that of fish fed the CON diet; which was used to the indication of fish maturation. During the spawning season, lipid granules and normal morphological structure were observed in the treated fish liver, whereas fewer lipid granules of liver were observed in the control group. Based on the immunity and stress resistance-related parameters such as hematological indices, antioxidant activity, lysozyme level, respiratory burst activity, blood reactive oxygen species (ROS), complement activity (ACH50 assay), specific IgM, brain AChE, plasma PGOT, and PGPT enzyme activity were significantly (P<0.01 and P<0.05) higher in fish fed the PBG diet than that of fish fed the CON diet. The fecundity, fertilization rate (92.23±2.69%), hatching rate (87.43±2.17 %) and survival (76.62±0.82%) of offspring were significantly higher (P˂0.05) in the PBG diet than in the control. Consequently, early embryonic and larval development was better in PBG treated group than in the control. Therefore, the present study showed that the polyunsaturated fatty acids (PUFAs) and beta glucan enriched experimental diet were more effective and achieved better growth, feed utilization, maturation, immunity, and spawning performances of O. pabda.

Keywords: polyunsaturated fatty acids, beta glucan, maturity, immunity, catfish

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Authors: Hosein Maghsoudi

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Rheumatois arthritis (RA) is progressive inflammatory autoimmune diseases that primarily affect the joints, characterized by synovial hyperplasia and inflammatory cell infiltration, deformed and painful joints, which can lead tissue destruction, functional disability systemic complications, and early dead and socioeconomic costs. The cause of rheumatoid arthritis is unknown, but genetic and environmental factors are contributory and the prognosis is guarded. However, advances in understanding the pathogenesis of the disease have fostered the development of new therapeutics, with improved outcomes. The current treatment strategy, which reflects this progress, is to initiate aggressive therapy soon after diagnosis and to escalate the therapy, guided by an assessment of disease activity, in pursuit of clinical remission. The pathobiology of RA is multifaceted and involves T cells, B cells, fibroblast-like synoviocyte (FLSc) and the complex interaction of many pro-inflammatory cytokine. Novel biologic agents that target tumor necrosis or interlukin (IL)-1 and Il-6, in addition T- and B-cells inhibitors, have resulted in favorable clinical outcomes in patients with RA. Despite this, at least 30% of RA patients are résistance to available therapies, suggesting novel mediators should be identified that can target other disease-specific pathway or cell lineage. Among the inflammatory cell population that might participated in RA pathogenesis, FLSc are crucial in initiaing and driving RA in concert of cartilage and bone by secreting metalloproteinase (MMPs) into the synovial fluid and by direct invasion into extracellular matrix (ECM), further exacerbating joint damage. Invasion of fibroblast-like synoviocytes (FLSc) is critical in the pathogenesis of rheumatoid-arthritis. The metalloproteinase (MMPs) and activator of Toll-like receptor 4 (TLR4)/nuclear factor- κB pthway play a critical role in RA-FLS invasion induced by lipopolysaccharide (LPS). The present study aimed to explore the anti-invasion activity of Glycyrrhizic Acid as a pharmacologically safe phytochemical agent with potent anti-inflammatory properties on IL-1beta and TNF-alpha signalling pathways in Bovine fibroblast-like synoviocyte ex- vitro, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Results showed that Glycyrrhizic Acid suppressed LPS-stimulated bovine FLS migration and invasion by inhibition MMP-9 expression and activity. In addition our results revealed that Glycyrrhizic Acid inhibited the transcriptional activity of MMP-9 by suppression the nbinding activity of NF- κB in the MMP-9 promoter pathway. The extract of licorice (Glycyrrhiza glabra L.) has been widely used for many centuries in the traditional Chinese medicine as native anti-allergic agent. Glycyrrhizin (GL), a triterpenoidsaponin, extracted from the roots of licorice is the most effective compound for inflammation and allergic diseases in human body. The biological and pharmacological studies revealed that GL possesses many pharmacological effects, such as anti-inflammatory, anti-viral and liver protective effects, and the biological effects, such as induction of cytokines (interferon-γ and IL-12), chemokines as well as extrathymic T and anti-type 2 T cells. GL is known in the traditional Chinese medicine for its anti-inflammatory effect, which is originally described by Finney in 1959. The mechanism of the GL-induced anti-inflammatory effect is based on different pathways of the GL-induced selective inhibition of the prostaglandin E2 production, the CK-II- mediated activation of both GL-binding lipoxygenas (gbLOX; 17) and PLA2, an anti-thrombin action of GL and production of the reactive oxygen species (ROS; GL exerts liver protection properties by inhibiting PLA2 or by the hydroxyl radical trapping action, leading to the lowering of serum alanine and aspartate transaminase levels. The present study was undertaken to examine the possible mechanism of anti-inflammatory properties GL on IL-1beta and TNF-alpha signalling pathways in bovine fibroblast-like synoviocyte ex-vivo, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Our results clearly showed that treatment of bovine fibroblast-like synoviocyte with GL suppressed LPS-induced cell migration and invasion. Furthermore, it revealed that GL inhibited the transcription activity of MMP-9 by suppressing the binding activity of NF-κB in the MM-9 promoter. MMP-9 is an important ECM-degrading enzyme and overexpression of MMPs in important of RA-FLSs. LPS can stimulate bovine FLS to secret MMPs, and this induction is regulated at the transcription and translational levels. In this study, LPS treatment of bovine FLS caused an increase in MMP-2 and MMP-9 levels. The increase in MMP-9 expression and secretion was inhibited by ex- vitro. Furthermore, these effects were mimicked by MMP-9 siRNA. These result therefore indicate the the inhibition of LPS-induced bovine FLS invasion by GL occurs primarily by inhibiting MMP-9 expression and activity. Next we analyzed the functional significance of NF-κB transcription of MMP-9 activation in Bovine FLSs. Results from EMSA showed that GL suppressed LPS-induced NF-κB binding to the MMP-9 promotor, as NF-κB regulates transcriptional activation of multiple inflammatory cytokines, we predicted that GL might target NF-κB to suppress MMP-9 transcription by LPS. Myeloid differentiation-factor 88 (MyD88) and TIR-domain containing adaptor protein (TIRAP) are critical proteins in the LPS-induced NF-κB and apoptotic signaling pathways, GL inhibited the expression of TLR4 and MYD88. These results demonstrated that GL suppress LPS-induced MMP-9 expression through the inhibition of the induced TLR4/NFκB signaling pathway. Taken together, our results provide evidence that GL exerts anti-inflammatory effects by inhibition LPS-induced bovine FLSs migration and invasion, and the mechanisms may involve the suppression of TLR4/NFκB –mediated MMP-9 expression. Although further work is needed to clarify the complicated mechanism of GL-induced anti-invasion of bovine FLSs, GL might be used as a further anti-invasion drug with therapeutic efficacy in the treatment of immune-mediated inflammatory disease such as RA.

Keywords: glycyrrhizic acid, bovine fibroblast-like synoviocyte, tlr4/nf-κb, metalloproteinase-9

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