The effect of hyperthyroidism on the levels of liver enzymes in adult male Wistar rats

 Thyrotoxicosis is a condition in which tissues are stimulated by increased secretion of thyroid hormone. The most common cause is diffuse toxic goiter and toxic multi-nodular goiter. For more reviews on this disease, the effects of hyperthyroidism on liver enzyme levels were studied. A total of 30 adult male Wistar rats weighing about 190 g were purchased from the Pasteur Institute of Iran. In this study, rats were divided into control group, the group receiving vitamin E, the group receiving levothyroxine, the group receiving levothyroxine treated with vitamin E; blood was taken from all groups over a period of 10 days after injection, and measurement of thyroid hormones and liver tests was made. The findings obtained in this study show that Isolated systolic hypertension (ISH) hormone levels in rats treated with levothyroxine, Treatment with vitamin E may reduce serum levels of ISH , Hormone levels of T4 in the rats treated with levothyroxine were increased compared to normal rates. Treatment with vitamin E reduces serum levels of T4 compared to the first hyper group. T4 hormone levels in rats treated with levothyroxine were reduced compared to normal rates. Treatment with vitamin E may reduce serum levels of T4 compared with the first hyper group. Asparagine Transferase (AST) enzyme levels in rats treated with levothyroxine were increased compared, Treatment with vitamin E may reduce serum levels of AST , Alanine transferase (ALT) enzyme levels in rats treated with levothyroxine were increased , Treatment with vitamin E may increase serum levels of ALT , alkaline phosphatase (ALP) enzyme levels in rats treated with levothyroxine has been increased compared with normal rates. Treatment with vitamin E resulted in serum levels of ALT not to be increased compared with the first group. According to the results of hyperthyroidism and levels of liver enzymes, it can be concluded that hyperthyroidism induced by levothyroxine can increase the levels of hormones T3, T4 and Thyroid Stimulating Hormone (TSH), and then increase the levels of liver enzymes. Treatment of empirical samples with vitamin E is likely to reduce liver damages and prevent the increased levels of liver enzymes compared to empirical samples of hyperthyroidism which have been treated with vitamin E.

Cloning and Expression of N-terminal Region of IpaD from Shigella dysenteriae in E. coli

Genus Shigella is one of the important members of the family enterobacteriacae. There are numerous antigens in Shigella carrying by a 220 kb plasmid. Among them, IpaD is the key virulence factor of S. flexneri. Apart from having effectors function that is essential for host cell invasion and intracellular survival, this protein also controls the secretion and translocation of other effector proteins into eukaryotic host cells. In the present study, we have cloned and expressed the ipaD in E. coli. The ipaD gene was amplified by PCR. Prokaryote expression vector pET-28a(+)- ipaD was constructed, and used to transform E. coli BL21DE3 plySs. The expression of recombinant protein induced by IPTG was examined by SDS-PAGE. Western blot were used to determine immunoreactivity of IpaD-His by a rabbit monoclonal antibodies against his-tag. SDS-PAGE demonstrated that the constructed prokaryotic expression efficiently produced IpaD at the 1 mmol/L of IPTG. IpaD protein was able to react with the rabbit monoclonal antibody against His-tag.  IpaD is essential for Shigella spp invasion. N-terminal region is most significant functional fragment of IpaD. Purification of IpaD from the wild type of Shigella is difficult furthermore profound study on a specific domain on the N-terminal of IpaD by using the wild type of purified IpaD is not feasible.

The Current Landscape of Glioblastoma Biomarkers in Body Fluids

Glioblastoma (GBM) is a highly aggressive and lethal primary brain cancer that necessitates early detection and accurate diagnosis for effective treatment and improved patient outcomes. Traditional diagnostic methods, such as imaging techniques and tissue biopsies, have limitations in providing real-time information and distinguishing treatment-related changes from tumor progression. Liquid biopsies, used to analyze biomarkers in body fluids, offer a non-invasive and dynamic approach to detecting and monitoring GBM. This article provides an overview of GBM biomarkers in body fluids, including circulating tumor cells (CTCs), cell-free DNA (cfDNA), cell-free RNA (cfRNA), microRNA (miRNA), and extracellular vesicles. It explores the clinical utility of these biomarkers for GBM detection, monitoring, and prognosis. Challenges and limitations in implementing liquid biopsy strategies in clinical practice are also discussed. The article highlights the potential of liquid biopsies as valuable tools for personalized GBM management but underscores the need for standardized protocols and further research to optimize their clinical utility

Detection of Sea, Seb, Sec, Seq genes in staphylococcus aureus isolated from nasal carriers in Tehran province, Iran; by multiplex PCR

Staphylococcus(S.) aureus  produces different extra-cellular protein toxins and virulence factors. One of the most important extra-cellular proteins is an enterotoxin which causes staphylococcal food poisoning (SFP) due to their enterotoxins. Different methods have been used to detect this toxin, each of which has advantages and disadvantages. DNA amplification methods, however, can show the presence of enterotoxigenic strains of S. aureus before the expression of enterotoxins on the basis of specific gene sequences. In this study, 150 S. aureus strains isolated from nasal carriers were confirmed by biochemical testing. PCR was used to amplify the staphylococcal enterotoxin A, B, C and Q genes, as well as the staphylococcal nuclease gene.  Among the 150 healthy human isolates from the nasal carrier, 95 were confirmed as S. aureus.  Only 58.9% of the isolates were diagnosed as sea, b, c, q positive. There were 24 (25.3%) isolates associated with the sea gene, 15.8% isolates associated with the seb gene, 9.5% of the isolates were associated with the sec gene, and 8.4% of the isolates associated with the seq gene. Of these isolates, 41% might be possessing additional se genes but they were not see (178 bp) and sed (319 bp) genes.  The nuc gene, which encodes thermo nuclease, was used as a target DNA to identify S. aureus. Additionally, one of these enterotoxigenic isolates carried more than one toxin gene

Synthesis and characterisation of aerosolised MIF inhitibitors for the treatment of respiratory disease

The main focus of this PhD thesis was to investigate the synthesis and characterisation of an aerosolised poly lactic-co-glycolic acid (PLGA) nanodrug delivery system for MIF enzyme inhibitors to modulate the physiological activity of macrophage migration inhibitory factor (MIF) in pulmonary diseases, particularly lung cancer. MIF is a proinflammatory mediator of the immune system that plays a substantial role in the overall inflammatory cascade, tumour growth, angiogenesis, and cancer progression. Recently, we have identified a novel drug candidate, SCD19, which showed convincing results in both in vitro and in vivo studies of lung cancer. Herein we report our work to maximise local delivery of MIF therapeutics directly to the lungs through the development of an aerosolised delivery system utilising state of the art nanoparticle-based drug delivery systems. Aerosolised nanoparticle delivery systems to the lung represent a novel future therapeutic strategy for cancer and in particular lung cancer. The use of aerosolised PLGA nanodrug delivery systems has increased markedly due to numerous advantages of this biodegradable, nontoxic and FDA approved nanodrug delivery system. Initially, we encapsulated SCD19 into PLGA nanospheres by employing single emulsion-solvent evaporation technique. Transmission electron microscopy (TEM) and scanning electron microscope (SEM) images of PLGA-SCD19 nanoparticles showed a uniform spherical shape with smooth surfaces. The average hydrodynamic size of the PLGA-SCD19 nanoparticles, as measured by using nanoparticle tracking analysis (NTA) was 200 nm without aggregation. The drug loading efficiency, yield efficiency, and the drug content were 63%, 66%, and 5.7%, respectively, which were within the acceptable range. The nanoparticles were found to be stable in both artificial lung fluid and artificial lysosomal fluid. For the internalisation study of the nanoparticles, we co-encapsulated iron oxide nanoparticles (magnetic nanoparticles (MNPs)) and SCD19 into PLGA nanoparticles to make PLGA-MNP-SCD19. Then, we carried out different methods to investigate the cellular uptake of the PLGA-MNP-SCD19, in all of which significant accumulations of nanoparticles occurred in the cells after overnight incubation. Biocompatibility and toxicity of the nanoformulation were evaluated with high content analysis and LDH assay. There was no attributable toxicity associated with the nanoparticles and they showed a high degree of biocompatibility in human A549, murine RAW 264.7, and LLC cell lines. In this study, we established a collaboration with Aerogen Ltd, a company specialising in the production of aerosol drug delivery devices. Initially, we optimised our nanoformulation for Aerogen?s vibrating mesh nebuliser to achieve maximum drug delivery within acceptable nebulisation times. The vibrating mesh nebuliser did not affect the size nor the volume of PLGA-SCD19 nanoparticles. Also, laser diffraction method showed that the nebulised nanoparticles had an acceptable volume mean diameter (VMD) with an optimal particle size distribution for deep lung deposition. This leads to improve treatment efficiency by allowing aerosols to access the small airways with minimum waste. Moreover, in our study, the regional deposition of the aerosol nanoparticles in a mechanical human respiratory tract model, resulted in high deposition (more than 70%) in the alveolar region of the lung model with very low deposition in upper respiratory tract. Further investigation was conducted to define drug delivery efficiency. In this study we achieved 23% and 14% drug delivery efficiency from the mechanical ventilator and the breathing simulator, respectively. However, previous studies of other compounds had shown a wide range of drug delivery efficiency (from 1% to 16%). Finally, we examined the ability of our aerosolised PLGA-SCD19 nanoparticles to reduce cell proliferation in a MIF-Induced cell growth in vitro model which resulted in a significant reduction of cell proliferation (***p 0.001) in the selected cancer cells. This study has demonstrated that the developed aerosolised nanodrug delivery system may provide a novel adjunctive agent for use with anticancer drugs in the treatment of patients with lung cancer and the data obtained from characterisation studies may contribute to future drug delivery research

Molecular Insight into the Therapeutic Effects of Stem Cell-Derived Exosomes in Respiratory Diseases and the Potential for Pulmonary Delivery

Respiratory diseases are the cause of millions of deaths annually around the world. Despite the recent growth of our understanding of underlying mechanisms contributing to the pathogenesis of lung diseases, most therapeutic approaches are still limited to symptomatic treatments and therapies that only delay disease progression. Several clinical and preclinical studies have suggested stem cell (SC) therapy as a promising approach for treating various lung diseases. However, challenges such as the potential tumorigenicity, the low survival rate of the SCs in the recipient body, and difficulties in cell culturing and storage have limited the applicability of SC therapy. SC-derived extracellular vesicles (SC-EVs), particularly SC-derived exosomes (SC-Exos), exhibit most therapeutic properties of stem cells without their potential drawbacks. Similar to SCs, SC-Exos exhibit immunomodulatory, anti-inflammatory, and antifibrotic properties with the potential to be employed in the treatment of various inflammatory and chronic respiratory diseases. Furthermore, recent studies have demonstrated that the microRNA (miRNA) content of SC-Exos may play a crucial role in the therapeutic potential of these exosomes. Several studies have investigated the administration of SC-Exos via the pulmonary route, and techniques for SCs and SC-Exos delivery to the lungs by intratracheal instillation or inhalation have been developed. Here, we review the literature discussing the therapeutic effects of SC-Exos against respiratory diseases and advances in the pulmonary route of delivery of these exosomes to the damaged tissues

Smart Nanotherapeutics and Lung Cancer

Lung cancer is a significant health problem worldwide. Unfortunately, current therapeutic strategies lack a sufficient level of specificity and can harm adjacent healthy cells. Consequently, to address the clinical need, novel approaches to improve treatment efficiency with minimal side effects are required. Nanotechnology can substantially contribute to the generation of differentiated products and improve patient outcomes. Evidence from previous research suggests that nanotechnology-based drug delivery systems could provide a promising platform for the targeted delivery of traditional chemotherapeutic drugs and novel small molecule therapeutic agents to treat lung cancer cells more effectively. This has also been found to improve the therapeutic index and reduce the required drug dose. Nanodrug delivery systems also provide precise control over drug release, resulting in reduced toxic side effects, controlled biodistribution, and accelerated effects or responses. This review highlights the most advanced and novel nanotechnology-based strategies, including targeted nanodrug delivery systems, stimuli-responsive nanoparticles, and bio-nanocarriers, which have recently been employed in preclinical and clinical investigations to overcome the current challenges in lung cancer treatments

سیاسة تعزیز العوامل المؤثرة في الإقبال علی الوقف و تعزیز دور المؤسسات الخیریة في الریاضة من أجل بسط العدالة الریاضیة و الإرتقاء بصحة المجتمع

سابقه و هدف: یکی از مهم‌ترین مسائلی که امروزه باید به آن توجه داشت تأثیر نقش وقف و امور خیریه در تأمین نیازهای فرهنگی، ورزشی، اجتماعی و اقتصادی جامعه است. اینکه وقف تا چه حد می­تواند در رفع کمبودها و شکوفایی ورزش کشور مفید واقع شود، نیازمند بحث و بررسی عمیق صاحب­نظران و کارشناسان حوزۀ ورزش است. هدف از انجام پژوهش حاضر ارائۀ الگوی عوامل مؤثر بر گسترش وقف و ورود خيران در حوزۀ ورزش بود. روش کار: این پژوهش از نوع کاربردی و به لحاظ راهبردی کمّی است. جامعۀ آماری شامل صاحب‌نظران این حوزه و مجمع خیّران سلامت و انجمن خیّران مدرسه‌‌ساز بود که به‌طور مستقیم با چالش‌ها و رهیافت‌های ورود خیّران در ورزش آشنایی داشتند. روش نمونه­گیری به‌صورت غيراحتمالي با انتخاب هدفمند و با حداکثر بیست تنوع یا ناهمگونی بود. بر این اساس 360 نفر نمونۀ پژوهش در نظر گرفته شدند. ابزار پژوهش شامل پرسش‌نامۀ مستخرج از مطالعات و بررسی مبانی نظری بود که هفت نفر از متخصصان روایی آن را تأیید کردند و پایایی آن با آزمون آلفای کرونباخ در حد مطلوب به اثبات رسید. در این پژوهش همۀ موارد اخلاقی رعایت شده است و مؤلفان مقاله تضاد منافعی گزارش نکرده‌اند. یافته‌ها: بر اساس نتایج تحلیل عامل تأییدی بارهای عاملی عوامل تشکیل‌دهنده بالاتر از 4/0 بود که تأیید می‌شود. همچنین شاخص­هاي ارزيابي کليت الگوی معادلۀ ساختاري با توجه به دامنۀ مطلوب اين شاخص­ها درمجموع بيانگر اين است که الگوی مفروض تدوين‌شده توسط داده­هاي پژوهش حمايت مي­شود. به عبارت ديگر، برازش داده­ها به الگو برقرار است و همگي شاخص­ها جز شاخص نسبت کای­اسکوئر به درجۀ آزادی دلالت بر مطلوبيت الگوی اندازه­گیری الگوی ورود خیّران در ورزش دارد. نتیجه‌گیری: ورود خیّران به ورزش می‌تواند نوعی جذب سرمایۀ مناسب باشد که فضاهای ورزشی استانداردی در همۀ نقاط کشور ساخته شود و همۀ آحاد جامعه به‌صورت مساوی از این اماکن استفاده نمایند. این امر با هدف توسعۀ ابعاد مختلف آن نیازمند پیوند با نهادهای دیگر ازجمله اقتصاد، بهداشت و سلامت، نظام تربیتی در سطح حاکمیت و سیاست­گذاری است تا با یادگیری سیاست‌های ورزشی الگو‌های کاربردی و متناسب را به کار گرفت.Background and Objective: One of the most important issues to be considered is the role of endowments and charity affairs in meeting the cultural, sports, social and economic needs of the society. To what extent that endowment can be useful in solving the problems and flourishing of the country's sports, requires deeper examination of issues by experts particularly the experts in the field of sports.The purpose of this study was to present a model of the factors affecting the expansion of endowment in the field of sports. Methods: The research is applied in terms of purpose and quantitative in terms of method. The statistical population included experts in this field and the Health Donors Association and the School-Building Donors Association, who were directly familiar with the challenges and ways of introducing donors into sports. The sampling method included non-probability sampling, with purposeful selection and with maximum 20 varieties or incongruity. Based on this, 360 participants were selected as the sample population. The research instrument included a questionnaire extracted from the previous studies and review of theoretical foundations, the validity of which was proved by 7 experts and its reliability was found based on Cronbach's alpha test to be at the desired level. In this study, all ethical considerations were observed and no conflict of interest was reported by the authors. Results: Based on the results of confirmatory factor analysis, the factor loads of the constituent factors were higher than 0.4 and were approved. Also, the evaluation indicators of the totality of the structural equation model according to the desired range of these indicators, in general, indicate that the hypothetical model developed by the research data is supported. In other words, the fit of the data to the model is established and all indicators except for the Chi-square ratio to the degree of freedom, are indicative of the desirability of the measurement model of the donor entry model in sports. Conclusion: The arrival of donors can be a good investment to build provincial sports facilities in all parts of the country so that all members of the society can use these places equally. With the aim of developing its various dimensions, this requires links with other institutions such as those in economy, health, education system at the level of governance and policy-making, to apply practical and appropriate models by learning about the sports policies.خلفية البحث وأهدافه: تعتبر دراسة تاثیر دور الوقف الدیني والأعمال الخیریة في تعزیز وتنمیة الشوؤن الثقافیة، والریاضیة، والإجتماعیة، والإقتصادیة، من أهم القضایا التي یجب الإهتمام بها والترکیز علیها. فدراسة دور الوقف الدیني وتأثیره علی التنمیة الریاضیة وتفعیل الطاقات والمواهب الریاضیة، أمر في غایة الأهمیة ولابد للمعنیین بهذا المجال من إیلاء الإهتمام اللازم بهذا الأمر الحیوي. تسعی هذه الدراسة إلی بلورة الدور الذي یمکن أن یلعبه الوقف الدیني والمؤسسات الخیریة في تطور الریاضة وتنمیة الطاقات الریاضیة. منهجية البحث: تعتمد هذه الدراسة علی المنهجیة الطبیقیة وتعتمد الکمیة. أما الإستبیان فقد أجري علی المتخصصین في هذا الشأن والجمعیة الخیریة ونادي بناة المدارس الخیریة. فقد أجریت مقابلات مع هؤلاء بشکل مباشر وتمت دراسة التحدیات والمشکال التي تواجها المؤسسات الخیریة في دخول هؤلاء الأفراد في هذا المجال. أما العیّنات فقد اختیرت بشکل عشوائي من بین عشرین عینة مختلفة. اعتمدت الدراسة علی آراء 360 شخصا من بین المشارکین في الإستیبان. أما أدوات البحث فقد شملت الإستفتاء والإستبیان الذي اعتمدته الدراسات المعنیة بالشؤون الریاضیة. وقد قام سبعة من المختصصین في العلوم الریاضیة بدراسة المبادئ الأساسیة لهذا المجال وأثبتت نجاعتها في تحلیل کرونباخ. تمت مراعاة جميع الموارد الأخلاقية في هذا البحث واضافة الى هذا فإن مؤلفي البحث لم يشيروا الى أي تضارب في المصالح. المعطیات: تشیر نتائج البحث أنّ العامل المحفز الذي یحث علی العمل یشکل 4/0 بالمئة و هو ما تقرّ به الدراسة. کما أنّ المؤشرات البحثیة التي بحثت صیاغة الدراسة بالنظر إلی الأهداف، تشیر إلی أنّ الأنموذج المصاغ عبر المعطیات هو أنموذج صائب تماماً. بتعبیر آخر تحلیل المعطیات تابع للأنموذج و کل المؤشرات سوی مؤشر کاي اسکوئر تشیر إلی ضرورة و نجاعة دخول المؤسسات الخیریة في الساحة الریاضیة. الاستنتاج: یمکن أن یؤدي دخول المؤسسات الخیریة في الساحة الریاضیة و إطلاق مشاریع ریاضیة إلی جذب الإستثمار وتعزیز البنیة التحتیة الریاضیة علی مستوی البلاد؛ وتمکن جمیع المواطنین من الإستفادة من هذه المشاریع والإمکانیات علی حد سواء. لکن هذا الهدف لا یتحقق إلّا بمشارکة المؤسسات الأخری کالمؤسسات الإقتصادیة، والصحیة وغیرها. فالمؤسسة الریاضیة لابد لها من إتخاذ سیاسات صارمة ودقیقة علی مستوی البلد حتی تتمکن من الإزدهار والنمو وإطلاق الطاقات الریاضیة

Synergistic effects of Para

Background and aim: Post-operative pain is considered an important complication of Intravenous regional anesthesia (IVRA) which is gaining popularity especially for surgeries on upper limbs. Methods: The present double blind randomized clinical trial was conducted on 60 candidates of upper limb surgeries aged between 20 and 60 years who were of ASA classes 1 or 2. Subjects were randomly assigned to 4 groups: the first group was treated solely with 3 mg/kg of Lidocaine. The second and third groups received the same amount of Lidocaine plus 8 mg of Dexamethasone or 300 mg of Paracetamol respectively and for the fourth group a combination of all medications was used. For all patients, Lidocaine was diluted with normal saline until a total volume of 40 cc was reached. Onset of Sensory and motor nerve blocks, severity of post-operative pain and amount of mepridine consumption in the first 24 h after surgery were assessed. Results: Onset of Sensory and motor nerve block was significantly accelerated in the fourth group (p < 0.01). Post-operative pain and analgesic consumption were significantly reduced in the fourth group when compared with the other groups (p < 0.05). Conclusion: A combination of Paracetamol and Dexamethasone significantly enhances the analgesic effect of Lidocaine in IVRA by accelerating the establishment of both the sensory and motor nerve blocks and prolonging the period of analgesia as well as improving the quality of analgesia and reducing the need for analgesic medications during and after the operation