Search results for: intestine and adipose tissue

Authors: Monisha Isaac

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Biotechnology is a discipline which explains the use of living organisms and systems to construct a product, or we can define it as an application or technology developed to use biological systems and organisms processes for a specific use. Particularly, it includes cells and its components use for new technologies and inventions. The tools developed can be further used in diverse fields such as agriculture, industry, research and hospitals etc. The 21^st century has seen a drastic development and advancement in biotechnology in India. Significant increase in Government of India’s outlays for biotechnology over the past decade has been observed. A sectoral break up of biotechnology-based companies in India shows that most of the companies are agriculture-based companies having interests ranging from tissue culture to biopesticides. Major attention has been given by the companies in health related activities and in environmental biotechnology. The biopharmaceutical, which comprises of vaccines, diagnostic, and recombinant products is the most reliable and largest segment of the Indian Biotech industry. India has developed its vaccine markets and supplies them to various countries. Then there are the bio-services, which mainly comprise of contract researches and manufacturing services. India has made noticeable developments in the field of bio industries including manufacturing of enzymes, biofuels and biopolymers. Biotechnology is also playing a crucial and significant role in the field of agriculture. Traditional methods have been replaced by new technologies that mainly focus on GM crops, marker assisted technologies and the use of biotechnological tools to improve the quality of fertilizers and soil. It may only be a small contributor but has shown to have huge potential for growth. Bioinformatics is a computational method which helps to store, manage, arrange and design tools to interpret the extensive data gathered through experimental trials, making it important in the design of drugs.

Keywords: biotechnology, advancement, agriculture, bio-services, bio-industries, bio-pharmaceuticals

Procedia PDF Downloads 237

Authors: A. Fomujong, P. Mobit, A. Ndlovu, R. Teboh

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Purpose: Film’s unique qualities, such as tissue equivalence, high spatial resolution, near energy independence and comparatively less expensive dosimeter, ought to make it the preferred and widely used in radiotherapy centers in low and middle income countries (LMICs). This, however, is not always the case, as other factors that are often maybe taken for granted in advanced radiotherapy centers remain a challenge in LMICs. We explored the unique qualities of film dosimetry that can make it possible for one Institution to benefit from another’s protocols via collaboration. Methods: For simplicity, two Institutions were considered in this work. We used a single batch of films (EBT-XD) and established a calibration protocol, including scan protocols and calibration curves, using the radiotherapy delivery system at Institution A. We then proceeded and performed patient-specific QA for patients treated on system A (PSQA-A-A). Films from the same batch were then sent to a remote center for PSQA on radiotherapy delivery system B. Irradiations were done at Institution B and then returned to Institution A for processing and analysis (PSQA-B-A). The following points were taken into consideration throughout the process (a) A reference film was irradiated to a known dose on the same system irradiating the PSQA film. (b) For calibration, we utilized the one-scan protocol and maintained the same scan orientation of the calibration, PSQA and reference films. Results: Gamma index analysis using a dose threshold of 10% and 3%/2mm criteria showed a gamma passing rate of 99.8% and 100% for the PSQA-A-A and PSQA-B-A, respectively. Conclusion: This work demonstrates that one could use established film dosimetry protocols in one Institution, e.g., an advanced radiotherapy center and apply similar accuracies to irradiations performed at another institution, e.g., a center located in LMIC, which thus encourages collaboration between the two for worldwide patient benefits.

Keywords: collaboration, film dosimetry, LMIC, radiotherapy, calibration

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Authors: Saeed Pourhassan, Nastaran Maghbouli

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Statement of the problem: The relationship between obesity and cardiovascular diseases has been studied widely(1). The distribution of fat tissue gained attention in relation to cardiovascular risk factors during lang-time research (2). American College of Cardiology/American Heart Association (ACC/AHA) is widely and the most reliable tool to be used as a cardiovascular risk (CVR) assessment tool(3). This study aimed to determine which anthropometric index is better in discrimination of high CVR patients from low risks using ACC/AHA score in addition to finding the best index as a CVR predictor among both genders in different races and countries. Methodology & theoretical orientation: The literature in PubMed, Scopus, Embase, Web of Science, and Google Scholar were searched by two independent investigators using the keywords "anthropometric indices," "cardiovascular risk," and "obesity." The search strategy was limited to studies published prior to Jan 2022 as full-texts in the English language. Studies using ACC/AHA risk assessment tool as CVR and those consisted at least 2 anthropometric indices (ancient ones and novel ones) are included. Study characteristics and data were extracted. The relative risks were pooled with the use of the random-effect model. Analysis was repeated in subgroups. Findings: Pooled relative risk for 7 studies with 16,348 participants were 1.56 (1.35-1.72) for BMI, 1.67(1.36-1.83) for WC [waist circumference], 1.72 (1.54-1.89) for WHR [waist-to-hip ratio], 1.60 (1.44-1.78) for WHtR [waist-to-height ratio], 1.61 (1.37-1.82) for ABSI [A body shape index] and 1.63 (1.32-1.89) for CI [Conicity index]. Considering gender, WC among females and WHR among men gained the highest RR. The heterogeneity of studies was moderate (α²: 56%), which was not decreased by subgroup analysis. Some indices such as VAI and LAP were evaluated just in one study. Conclusion & significance: This meta-analysis showed WHR could predict CVR better in comparison to BMI or WHtR. Some new indices like CI and ABSI are less accurate than WHR and WC. Among women, WC seems to be a better choice to predict cardiovascular disease risk.

Keywords: obesity, cardiovascular disease, risk assessment, anthropometric indices

Procedia PDF Downloads 103

Authors: Zahra F. Al-Khateeb, Shenel Shekerzade, Hasna Boumenar, Siân M. Henson, Jordi L. Tremoleda, A. T. Michael-Titus

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Traumatic brain injury (TBI) is the leading cause of disability and death in young adults and also increases the risk ofneurodegeneration. The mechanisms linking moderate to severe TBI to neurodegeneration are not known. It has been proposed that cellular senescence inductionpost-injury could amplify neuroinflammation and induce long-term changes. The impact of these processes after injury to an immature brain has not been characterised yet. We carried out a controlled cortical impact injury (CCI) in juvenile 1 month-old male CD1 mice. Animals were anesthetised and received a unilateral CCI injury. The sham group received anaesthesia and had a craniotomy. A naïve group had no intervention. The brain tissue was analysed at 5 days and 35 days post-injury using immunohistochemistry and markers for microglia, astrocytes, and senescence. Compared tonaïve animals, injured mice showed an increased microglial and astrocytic reaction early post-injury, as reflected in Iba1 and GFAP markers, respectively; the GFAP increase persisted in the later phase. The senescence analysis showed a significant increase inγH2AX-53BP1 nuclear foci, 8-oxoguanine, p19ARF, p16INK4a, and p53 expression in naïve vs. sham groups and naïve vs. CCI groups, at 5 dpi. At 35 days, the difference was no longer statistically significant in all markers. The injury induced a decrease p21 expression vs. the naïve group, at 35 dpi. These results indicate the induction of a complex senescence response after immature brain injury. Some changes occur early and may reflect the activation/proliferation of non-neuronal cells post-injury that had been hindered, whereas changes such as p21 downregulation may reflect a delayed response and pro-repair processes.

Keywords: cellular senescence, traumatic brain injury, brain injury, controlled cortical impact

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Authors: Syed Ameer Haider Jafri

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The primary goal of a root canal treatment in deciduous teeth is to eliminate infection and to retain the tooth in a functional state until it gets physiologically exfoliated and replaced by permanent successor. Important requisite of a root canal filling material for primary teeth is that, it should resorb at a similar rate as the roots of primary tooth, be harmless to the periapical tissue and to the permanent tooth germ, resorb readily if pushed beyond the apex, be antiseptic, radio-opaque, should not shrink, adhere to the walls, not discolor the tooth and easy to fill & remove, if required at any stage. Presently available, commonly used obturating materials for primary teeth are zinc oxide eugenol, calcium hydroxide and iodoform based pastes. None of these materials so far meet the ideal requirement of root canal filling material. So in search of ideal obturating material, this study was planed, in which mixture of calcium hydroxide, zinc oxide & sodium fluoride and mixture of calcium hydroxide & sodium fluoride was compared clinically and radiographically with calcium hydroxide for the obturation of root canals of 75 carious exposed primary mandibular second molars of 59 children aged 4-9 years. All the three material shows good results, but after a follow-up of 9 months mixture of calcium hydroxide, two percent sodium fluoride & zinc oxide powder closely follow the resorption of root, mixture of calcium hydroxide, two percent sodium fluoride follow resorption of root in the beginning but later on majority of cases shows faster resorption whereas calcium hydroxide starts depleting from the canal from the beginning even as early as 3 months. Thus mixture of calcium hydroxide, two percent sodium fluoride & zinc oxide found to be best obturaring material for primary tooth.

Keywords: obturating material, primary teeth, root canal treatment, success rate

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Authors: Sally A. El Awdan

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Objective and Design: The purpose of this study was to evaluate the anti inflammatory, anti-arthritic and analgesic effects of antidepressants. Methods: Carrageenan model was used to assess effect on acute inflammation. Paw volume were measured at 1, 2, 3 and 4th hour post challenge. Anti-nociceptive effect was evaluated by hot plate method. Chronic inflammation was developed using Complete Freund's Adjuvant (CFA). The animals were injected with Freund’s adjuvant in sub-plantar tissue of the right posterior paw. Paw volume, ankle flexion scores, adjuvant-induced hyperalgesia and serum cytokine levels were assessed. Results: Results obtained demonstrate that mirtazapine, venalfaxine and escitalopram significantly and dose-dependently inhibited carrageenan-induced rat paw oedema. Mirtazapine, venalfaxine and escitalopram increased the reaction time of rats in hot plate test. We observed an increase in paw volume, ankle flexion scores, thermal hyperalgesia, serum levels of interleukin-1β, PGE2 and TNF-α, induced by intraplantar CFA injection. Regular treatment up to 28 days of adjuvant-induced arthritic rats with mirtazapine, venalfaxine and escitalopram showed anti anti-inflammatory and analgesic activities by suppressing the paw volume, recovering the paw withdrawal latency, and by inhibiting the ankle flexion scores in CFA-induced rats. In addition significant reduction in serum levels of interleukin-1β, PGE2 and TNF-α level in arthritic rats was reduced by treatment with drugs. Conclusion: These results suggest that antidepressants have significant anti-inflammatory and anti-nociceptive effects in acute and chronic models in rats, which may be associated with the reduction of interleukin-1β, PGE2 and TNF-α levels.

Keywords: antidepressants, carrageenan, anti-nociceptive, Complete Freund's Adjuvant

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Authors: Sukwoong Kang

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Background: The application of light-emitting diode (LED)-dependent photobiomodulation (PBM) in promoting post-tendon injury healing has been recently reported. Despite the establishment of a theoretical basis for ligament restoration through PBM, the lack of any empirical evidence deems this therapeutic strategy contentious. Therefore, the aim of this study was to investigate the potency of LED-based PBM in facilitating tendon healing in a murine model. Methods: Migration kinetics were analyzed at two specific wavelengths: 630 and 880 nm. The Achilles tendon in the hind limbs of Balb/c mice was severed via Achilles tendon transection. Subsequently, the mice were randomized into LED non-irradiation and LED irradiation groups. Mice with intact tendons were employed as healthy controls. The wounds were LED-irradiated for 20 min daily for two days. Histological properties, tendon healing mediators, and inflammatory mediators were screened on day 14. Results: The roundness of the nuclei and fiber structure, indicating the degree of infiltrated inflammatory cells and severity of fiber fragmentation, respectively, were considerably lower in the LED irradiation group than in the LED non-irradiation group. Immunohistochemical analysis depicted an increase in tenocytes (SCX+ cells) and a recovery of wounds with reduced fibrosis (lower collagen 3 and TGF-β1) in the LED irradiation group during healing; conversely, the LED non-irradiation group exhibited tissue fibrosis. The ratio of M2 macrophages to total macrophages was higher in the LED irradiation group than in the injured group. Conclusion: LED-based PBM in the Achilles tendon rupture murine model effectuated a rapid restoration of histological and immunochemical outcomes. The aforementioned findings suggest that LED-based PBM presents remarkable potential as an adjunct therapeutic for tendon healing and warrants further research to standardize various parameters to advance and establish it as a reliable treatment regime.

Keywords: photobiomodulation, light-emitting diode, tendon, regeneration

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Authors: Shaojun Zheng, Lei Xu, Yunzi Wang

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The main purpose of the research is to use the cultural ecology to analyze the renewal of Shenzhen urban village in the process of China's urbanization and to evaluate and guide the renewal, which will combine the society value and economic efficiency and activate urban villages. The urban village has a long history. There are also many old buildings, various residents, and a strong connection with the surrounding environment. Cultural ecology, which uses the knowledge of ecology to study culture, provides us a cultural perspective in the renewal. We take Hubei village in Shenzhen as our example. By using cultural ecology, we find a new way dealing with the relationship between culture and other factors. It helps us to give the buildings and space the culture meanings from different scales. It enables us to find a unique development pattern of urban village. After analyzing several famous cultural blocks cases, we find it is possible to connect the unique culture of urban village with the renovation of its buildings, community, and commerce. We propose the following strategies with specific target: 1. Building renovation: We repair and rebuild the origin buildings as little as possible, and retain the original urban space tissue as much as possible to keep the original sense of place and the cultural atmosphere. 2. Community upgrade: We reshape the village stream, fix the original function, add event which will activate people to complete the existing cultural circle 3. District commerce: We implant food and drink district, boutique commercial, and creative industries, to make full use of the historical atmosphere of the site to enhance the culture feelings For the renewal of a seemingly chaotic mixed urban village, it is important to break out from the conventional practices of building shopping malls or residential towers. Without creating those building landmarks, cultural ecology activates the urban village by exploiting its unique culture, which makes the old and new combine and becomes a new stream of energy, forming the new cultural, commercial and stylish landmark of the city.

Keywords: cultural ecology, urban village, renewal, combination

Procedia PDF Downloads 394

Authors: Ziyad S. Haidar

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Millions of teeth are removed annually, and dental extraction is one of the most commonly performed surgical procedures globally. Whether due to caries, periodontal disease or trauma, exodontia and the ensuing wound healing and bone remodeling processes of the resultant socket (hole in the jaw bone) usually result in serious deformities of the residual alveolar osseous ridge and surrounding soft tissues (reduced height/width). Such voluminous changes render the placement of a proper conventional bridge, denture or even an implant-supported prosthesis extremely challenging. Further, most extractions continue to be performed with no regard for preventing the onset of alveolar osteitis (also known as dry socket, a painful and difficult-to-treat/-manage condition post-exodontia). Hence, such serious resorptive morphological changes often result in significant facial deformities and a negative impact on the overall Quality of Life (QoL) of patients (and oral health-related QoL), alarming, particularly for the geriatric with compromised healing and in light of the thriving longevity statistics. Opportunity: Despite advances in tissue/wound grafting, serious limitations continue to exist, including efficacy and clinical outcome predictability, cost, treatment time, expertise and risk of immune reactions. For cases of dry sockets, specifically, the commercially-available and often-prescribed home remedies are highly lacking. Indeed, most are not recommended for use anymore. Alveogyl is a fine example. Hence, there is a great market demand and need for alternative solutions. Solution: Herein, SockGEL/PLUG (patent pending), an all-natural, drug-free and injectable stimuli-responsive hydrogel, was designed, formulated, characterized and evaluated as an osteogenic, angiogenic, anti-microbial and pain-soothing suture-free intra-alveolar dressing, safe and efficacious for use in several oro-dental and cranio-maxillo-facial interventional applications; for example: in fresh dental extraction sockets, immediately post-exodontia. It is composed of FDA-approved, biocompatible and biodegradable polymers, self-assembled electro-statically to formulate a scaffolding matrix to (a) prevent the onset of alveolar osteitis via securing the fibrin-clot in situ and protecting/sealing the socket from contamination/infection; and (b) endogenously promote/accelerate wound healing and bone remodeling to preserve the volume of the alveolus. Findings: The intrinsic properties of the SockGEL/PLUG hydrogel were evaluated physico-chemico-mechanically for safety (cell viability), viscosity, rheology, bio-distribution and essentially, capacity to induce wound healing and osteogenesis (small defect, in vivo) without any signaling cues from exogenous cells, growth factors or drugs. The performed animal model of cranial critical-sized and non-vascularized bone defects shall provide vitally critical insights into the role and mechanism of the employed natural bio-polymer blend and gel product in endogenous reparative regeneration of soft tissues and bone morphogenesis. Alongside, the fine-tuning of our modified formulation method will further tackle appropriateness, reproducibility, scalability, ease and speed in producing stable, biodegradable and sterilizable stimuli (thermo-sensitive and photo-responsive) matrices (3-dimensional interpenetrating yet porous polymeric network) suitable for an intra-socket application, and beyond. Conclusions and Perspective: Findings are anticipated to provide sufficient evidence to translate into pilot clinical trials and validate the bionanomaterial before engaging the market for feasibility, acceptance and cost-effectiveness studies. The SockGEL/PLUG platform is patent pending: SockGEL is a bio-inspired drug-free hydrogel; SockPLUG is a drug-loaded hydrogel designed for complex indications.

Keywords: hydrogel, injectable, dentistry, craniomaxillofacial complex, bioinspired, nanobiotechnology, biopolymer, sol-gel, stimuli-responsive, matrix, tissue engineering, regenerative medicine

Procedia PDF Downloads 75

Authors: A. Lubis, R. Widayanti, Z. Hikmah, A. Endaryanto, A. Harsono, A. Harianto, R. Etika, D. K. Handayani, M. Sampurna

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Neonatal lupus erythematous (NLE) is a rare disease marked by clinical characteristic and specific maternal autoantibody. Many cutaneous, cardiac, liver, and hematological manifestations could happen with affect of one organ or multiple. In this case, both babies were premature, low birth weight (LBW), small for gestational age (SGA) and born through caesarean section from a systemic lupus erythematous (SLE) mother. In the first case, we found a baby girl with dyspnea and grunting. Chest X ray showed respiratory distress syndrome (RDS) great I and echocardiography showed small atrial septal defect (ASD) and ventricular septal defect (VSD). She also developed anemia, thrombocytopenia, elevated C-reactive protein, hypoalbuminemia, increasing coagulation factors, hyperbilirubinemia, and positive blood culture of Klebsiella pneumonia. Anti-Ro/SSA and Anti-nRNP/sm were positive. Intravenous fluid, antibiotic, transfusion of blood, thrombocyte concentrate, and fresh frozen plasma were given. The second baby, male presented with necrotic tissue on the left ear and skin rashes, erythematous macula, athropic scarring, hyperpigmentation on all of his body with various size and facial haemorrhage. He also suffered from thrombocytopenia, mild elevated transaminase enzyme, hyperbilirubinemia, anti-Ro/SSA was positive. Intravenous fluid, methyprednisolone, intravenous immunoglobulin (IVIG), blood, and thrombocyte concentrate transfution were given. Two cases of neonatal lupus erythematous had been presented. Diagnosis based on clinical presentation and maternal auto antibody on neonate. Organ involvement in NLE can occur as single or multiple manifestations.

Keywords: neonatus lupus erythematous, maternal autoantibody, clinical characteristic, multiple organ manifestation

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Authors: Faisal A. Salih

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Vinpocetine (Vin) is an ethyl ester of apovincamic acid and is a semisynthetic derivative of vincamine, an alkaloid from plants of the genus Periwinkle (plant) vinca minor. It was found that this compound stimulates cerebral metabolism: it increases the uptake of glucose and oxygen, as well as the consumption of these substances by the brain tissue. Vinpocetine enhances the flow of blood in the brain and has a vasodilating, antihypertensive, and antiplatelet effect. Vinpocetine seems to improve the human ability to acquire new memories and restore memories that have been lost. This drug has been clinically used for the treatment of cerebrovascular disorders such as stroke and dementia memory disorders, as well as in ophthalmology and otorhinolaryngology. It has no side effects, and no toxicity has been reported when using vinpocetine for a long time. For the quantitative determination of Vin in dosage forms, the HPLC methods are generally used. A promising alternative is potentiometry with Vin- selective electrode, which does not require expensive equipment and materials. Another advantage of the potentiometric method is that the pills and solutions for injections can be used directly without separation from matrix components, which reduces both analysis time and cost. In this study, it was found that the choice of a good plasticizer an electrode with the following membrane composition: PVC (32.8 wt.%), ortho-nitrophenyl octyl ether (66.6 wt.%), tetrakis-4-chlorophenyl borate (0.6 wt.%) exhibits excellent analytical performance: lower detection limit (LDL) 1.2•10⁻⁷ M, linear response range (LRR) 1∙10⁻³–3.9∙10⁻⁶ M, the slope of the electrode function 56.2±0.2 mV/decade). Vin masses per average tablet weight determined by direct potentiometry (DP) and potentiometric titration (PT) methods for the two different sets of 10 tablets were (100.35±0.2–100.36±0.1) mg for two sets of blister packs. The mass fraction of Vin in individual tablets, determined using DP, was (9.87 ± 0.02–10.16 ±0.02) mg, while the RSD was (0.13–0.35%). The procedure has very good reproducibility, and excellent compliance with the declared amounts was observed.

Keywords: vinpocetine, potentiometry, ion selective electrode, pharmaceutical analysis

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Authors: Mahmoud S. Zaghloul, Mohammed M. Khalaf, Wael N. Thabet, Haidy N. Asham

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Background. Hypertrophic scarring is a difficult problem for burn patients, and scar management is an essential aspect of outpatient burn therapy. Post-burn pathologic scars involve functional and aesthetic limitations that have a dramatic influence on the patient’s quality of life. The aim was to investigate the use of extracorporeal shock wave therapy (ESWT), which targets the fibroblasts in scar tissue, as an effective modality for scar treatment in burn patients. Subjects and methods: forty patients with post-burn scars were assigned randomly into two equal groups; their ages ranged from 20-45 years. The study group received ESWT and traditional physical therapy program (deep friction massage, stretching exercises). The control group received traditional physical therapy program (deep friction massage, stretching exercises). All groups received two sessions per week for six successful weeks. The data were collected before and after the same period of treatment for both groups. Evaluation procedures were carried out to measure scar thickness using ultrasonography and Vancouver Scar Scale (VSS) was completed before and after treatment. Results: Post-treatment results showed that there was a significant improvement difference in scar thickness in both groups in favor of the study group. Percentage of improvement in scar thickness in the study group was 42.55%, while it was 12.15% in the control group. There was also a significant improvement difference between results obtained using VSS in both groups in favor of the study group. Conclusion: ESWT is effective in management of pathologic post burn scars.

Keywords: extracorporeal shock wave therapy, post-burn scars, ultrasonography, Vancouver scar scale

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Authors: Li-Ting Huang, Yu-Hsiang Shen, Cing-Ciao Ke, Sheng-Pin Tseng, Fan-Pin Tseng, Yu-Ching Ni, Chia-Yu Lin

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Chest radiography is the most common technique for the diagnosis and follow-up of pulmonary diseases. However, the lesions superimposed with normal structures are difficult to be detected in chest radiography. Chest tomosynthesis is a relatively new technique to obtain 3D section images from a set of low-dose projections acquired over a limited angular range. However, there are some limitations with chest tomosynthesis. Patients undergoing tomosynthesis have to be able to hold their breath firmly for 10 seconds. A digital tomosynthesis system with advanced reconstruction algorithm and high-stability motion mechanism was developed by our research group. The potential for the system to perform a bidirectional chest scan within 10 seconds is expected. The purpose of this study is to realize the influences of the scan speed on the image quality for our digital tomosynthesis system. The major factors that lead image blurring are the motion of the X-ray source and the patient. For the fore one, an experiment of imaging a chest phantom with three different scan speeds, which are 6 cm/s, 8 cm/s, and 15 cm/s, was proceeded to understand the scan speed influences on the image quality. For the rear factor, a normal SD (Sprague-Dawley) rat was imaged with it alive and sacrificed to assess the impact on the image quality due to breath motion. In both experiments, the profile of the ROIs (region of interest) and the CNRs (contrast-to-noise ratio) of the ROIs to the normal tissue of the reconstructed images was examined to realize the degradations of the qualities of the images. The preliminary results show that no obvious degradation of the image quality was observed with increasing scan speed, possibly due to the advanced designs for the hardware and software of the system. It implies that higher speed (15 cm/s) than that of the commercialized tomosynthesis system (12 cm/s) for the proposed system is achieved, and therefore a complete chest scan within 10 seconds is expected.

Keywords: chest radiography, digital tomosynthesis, image quality, scan speed

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Authors: Mohammad Alkhatatbeh, Nehad Ayoub, Nizar Mhaidat, Nesreen Saadeh, Lisa Lincz

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CD36 is involved in the development of atherosclerosis by enhancing macrophage endocytosis of oxidized-low density lipoproteins and foam cell formation. Soluble CD36 (sCD36) was found to be elevated in type 2 diabetic patients and was supposed to act as a marker of insulin resistance and atherosclerosis. In young subjects, sCD36 was associated with cardiovascular risk factors including obesity and hypertriglyceridemia. This study was conducted to further investigate the relationship between plasma sCD36 and cardiovascular risk factors among middle-aged patients with metabolic syndrome (MetS) and healthy controls. SCD36 concentrations were determined by enzyme-linked immunosorbent assays (ELISA) for 41 patients with MetS and 36 healthy controls. Data for other variables were obtained from patients' medical records. SCD36 concentrations were relatively low compared to most other studies and were not significantly different between the MetS group and controls (P-value=0.17). SCD36 was also not correlated with age, body mass index, glucose, lipid profile, serum electrolytes and blood counts. SCD36 was not significantly different between subjects with obesity, hyperglycemia, dyslipidemia, hypertension or cardiovascular disease and those without these abnormalities (P-value > 0.05). The inconsistency between results reported in this study and other studies may be unique to the study population or be a result of the lack of a reliable standardized method for determining absolute sCD36 concentrations. However, further investigations are required to assess CD36 tissue expression in the study population and to assess the accuracy of various commercially available sCD36 ELISA kits. Thus, the availability of a standardized simple sCD36 ELISA that could be performed in any basic laboratory would be more favorable to the specialized flow cytometry methods that detect CD36+ microparticles if it was to be used as a biomarker.

Keywords: metabolic syndrome, CD36, cardiovascular risk, obesity, type 2 diabetes mellitus

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Authors: Hamida Memon, Muhammad Sanan

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A 34-year-old male with no prior health issues presented with a wound in his left leg exhibiting active pus discharge, intense inflammation, pain radiating from the buttocks to the knee, foot drop, and skin darkening. Four years prior, he sustained an untreated dislocation of the hip joint and acetabulum from a road traffic accident. Initial nerve conduction studies (NCS) and electromyography (EMG) revealed severe axonotomesis of the left sciatic nerve and reduced compound muscle action potential in the left common peroneal nerve. Despite normal venous flow, edema and cellulitis were noted. Follow-up NCS/EMG in 2022 showed improvement, but in 2023, the patient experienced recurrent infection and underwent surgical intervention with tissue culture. Postoperative care included antibiotics and pain management. NCS/EMG in 2024 indicated decreased nerve amplitudes and conduction velocities, consistent with moderate axonotmesis and ongoing recovery, alongside incidental right S1 radiculopathy. General lab tests and abdominal imaging were normal. The patient was treated with Pregabalin and Neurobion for neuropathic pain and nerve support and is currently under observation by a tertiary sector hospital for treatment. This case underscores the critical importance of prompt treatment for hip dislocations to prevent long-term complications such as neuropathy and avascular necrosis. Delays in treatment significantly increase the risk of severe outcomes, highlighting the need for timely intervention. Overall, the case illustrates the challenges of managing complex nerve injuries and the importance of comprehensive care for optimal recovery.

Keywords: sciatic nerve neuropathy, hip dislocation, acetabular fracture, radiculopathy

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Authors: Abdela Bulbula

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Background: Marek’s disease virus is a devastating infection, causing high morbidity and mortality in chickens in Ethiopia. Methods: The current study was conducted from March to November, 2021 with the general objective of performing antemortem and postmortem, isolation, and molecular detection of Marek’s disease virus from outbreak cases in southwestern Ethiopia. Accordingly, based on outbreak information reported from the study sites namely, Bedelle, Yayo, and Bonga towns in southwestern Ethiopia, 50 sick chickens were sampled. The backyard and intensive farming systems of chickens were included in the sampling and priorities were given for chickens that showed clinical signs that are characteristics of Marek’s disease. Results: By clinical examinations, paralysis of legs and wings, gray eye, loss of weight, difficulty in breathing, and depression were recorded on all chickens sampled for this study and death of diseased chickens was observed. In addition, enlargement of the spleen and gross lesions of the liver and heart were recorded during postmortem examination. The death of infected chickens was observed in both vaccinated and non-vaccinated flocks. Out of 50 pooled feather follicle samples, Marek’s disease virus was isolated from 14/50 (28%) by cell culture method and out of six tissue samples, the virus was isolated from 5/6(83.30%). By Real time polymerization chain reaction technique, which was targeted to detect the Meq gene, Marek’s disease virus was detected from 18/50 feather follicles which accounts for 36% of sampled chickens. Conclusion: In general, the current study showed that the circulating Marek’s disease virus in southwestern Ethiopia was caused by the oncogenic Gallid herpesvirus-2 (Serotype-1). Further research on molecular characterization of revolving virus in current and other regions is recommended for effective control of the disease through vaccination.

Keywords: Ethioi, Marek's disease, isolation, molecular

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Authors: Ana Claudia Muniz Rennó, Karina Nogueira

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This study aimed to investigate the in vivo tissue response of the introduction of the bioactive mesh (BM) scaffolds using a model of tibial bone defect implants in rats. Although a previous in vivo study demonstrated a highly positive response of particulate bioactive materials in the morphological and biomechanical properties of the bone callus, the effects of material with superior bioactivity, present in form of meshes have not been studied yet. Eighty male Wistar rats with 3 mm tibial defects were used. Animals were divided into four groups: intact group (IG) – tibia without any injury; bone defect day zero (0dD) – bone defects, sacrificed immediately after injury; bone defect control group (CG) – bone defects without any filler and bone defect filled with BM scaffold. The animals of BM and CG groups were sacrificed 15, 30 and 45 days post-injury to compare the temporal-special effects of the scaffolds on bone healing. The histological analysis revealed an organized newly formed bone at 30 and 45 days post-surgery in the BM. Also, this group presented an increased COX-2 expression on days 15 and 30 post-surgery. Furthermore, the immunohistochemistry analysis revealed that, BM presented a positive immunoexpression of RUNX-2 during all periods evaluated. The biomechanical analysis revealed that at 15 day after surgery, no significant statistically difference was observed between BM and CG and both groups had significantly higher values of maximal load compared to 0dG and significantly lower values than IG. On days 30 and 45 post-surgery, BM presented statistically lower values of maximal load compared to the CG. Nevertheless, at the same periods, BM did not show statistically significant difference compared to the IG maximal load values (p > 0, 05). Our results revealed that the implantation of the BM scaffolds was effective in stimulating newly bone formation.

Keywords: bone, biomaterials, scaffolds, cartilage

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Authors: Asieh Abbassi Daloii, Ahmad Abdi

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Introduction: Sports information suggests that physical inactivity increases the risk of many diseases, including atherosclerosis. Coronary heart disease, stroke and peripheral vascular disease, atherosclerosis and clinical protests. However, exercise can have beneficial effects on risk factors for atherosclerosis by reducing hyperlipidemia, hypertension, obesity, plaque density, increased insulin sensitivity and glucose tolerance is improved. Despite these findings, there is little information about the molecular mechanisms of interaction between the body and its relation to sport and there arteriosclerosis. The present study aims to investigate the effect of six weeks of progressive aerobic training and aqueous extract of crataegus monogyna on vascular endothelial growth factor (VEGF) variations and angiopoetin-1/2 (ANG- 1/2) in plasma and heart tissue in male Wistar rats. Methods: 30 male Wistar rats, 4-6 months old, were randomly divided into four groups: control crataegus monogyna (N=8), training crataegus monogyna (N=8), control saline (N=6), and training saline (N=8). The aerobic training program included running on treadmill at the speed of 34 meters per minute for 60 minutes per day. The training was conducted for six weeks, five days a week. Following each training session, both experimental and control subjects of crataegus monogyna groups were orally fed with 0.5 mg crataegus monogyna extract per gram of the body weight. The normal saline group was given the same amount of the normal saline solution (NS). Eventually, 72 hours after the last training session, blood samples were taken from inferior Verna cava. Conclusion: It is likely that crataegus monogyna extract compared with aerobic training and even combination of both training and crataegus monogyna extract is more effective on angiogenesis.

Keywords: angiopoietin 1, 2, vascular endothelial growth factor, aerobic exercise

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Authors: Navpreet Kaur, Randhir Singh

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Diabetic neuropathy is one of the most common microvascular complications of diabetes mellitus which affects more than 50% of diabetic patients. The present study targeted oxidative stress mediated nerve damage in diabetic rats using a hydro-alcohol extract of Cucurbita pepo L. (Family: Cucurbitaceae) and its potential in treatment of diabetic neuropathy. Diabetes neuropathy was induced in Wistar rats by injection of streptozotocin (65 mg/kg, i.p.) 15 min after Nicotinamide (230 mg/kg, i.p.) administration. Hydro-alcohol extract of C. pepo seeds was assessed by oral administration at 100, 200 and 400 mg/kg in STZ-nicotinamide induced diabetic rats. Thermal hyperalgesia (Eddy's hot plate and tail immersion), mechanical hyperalgesia (Randall-Selitto) and tactile allodynia (Von Frey hair tests) were evaluated in all groups of streptozotocin diabetic rats to assess the extent of neuropathy. Tissue (sciatic nerve) antioxidant enzymes (SOD, CAT, GSH and LPO) levels were measured along with the formation of AGEs in serum to assess the effect of hydro-alcohol extract of C. pepo in ameliorating oxidative stress. Diabetic rats exhibited significantly decreased tail-flick latency in the tail-immersion test and decreased paw withdrawal threshold in both Randall-Selitto and von-Frey hair test. A decrease in the nociceptive threshold was accompanied by significantly increased oxidative stress in sciatic nerve of diabetic rats. Treatment with the C. pepo hydro-alcohol extract significantly attenuated all the behavioral and biochemical alterations in a dose-dependent manner. C. pepo attenuated the diabetic condition and also reversed neuropathic pain through modulation of oxidative stress and thus it may find application as a possible therapeutic agent against diabetic neuropathy.

Keywords: advanced glycation end products, antioxidant enzymes, cucurbita pepo, hyperglycemia

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Authors: Meltem Haktaniyan, Eda Cagli, Irem Erel Goktepe

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Polymers that change their properties in response to different stimuli (e.g. light, temperature, pH, ionic strength or magnetic field) are called ‘smart’ or ‘stimuli-responsive polymers’. These polymers have been widely used in biomedical applications such as sensors, gene delivery, drug delivery or tissue engineering. Temperature-responsive polymers have been studied extensively for controlled drug delivery applications. As regard of pseudo-peptides, poly (2-alky-2-oxazoline)s are considered as good candidates for delivery systems due to their stealth behavior and nontoxicity. In order to build responsive multilayer films for controlled drug release applications from surface, Layer by layer technique (LBL) is a powerful technique with an advantage of nanometer scale control over spatial architecture and morphology. Multilayers can be constructed on surface where non-covalent interactions including electrostatic interactions, hydrogen bonding, and charge-transfer or hydrophobic-hydrophobic interactions. In the present study, hydrogen bounded multilayer films of poly (2-alky-2-oxazoline) s with tannic acid were prepared in order to use as a platform to release Doxorubicin (DOX) from surface with pH and thermal triggers. For this purpose, poly (2-isopropyl-2-oxazoline) (PIPOX) and poly (2-ethyl-2-oxazoline) (PETOX) were synthesized via cationic ring opening polymerization (CROP) with hydroxyl end groups. Two polymeric multilayer systems ((PETOX)/(DOX)-(TA) complexes and (PIPOX)/(DOX)-(TA) complexes) were designed to investigate of controlled release of Doxorubicin (DOX) from surface with pH and thermal triggers. The drug release profiles from the multilayer thin films with alterations of pH and temperature will been examined with UV-Vis Spectroscopy and Fluorescence Spectroscopy.

Keywords: temperature responsive polymers, h-bonded multilayer films, drug release, polyoxazoline

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Authors: Yinebeb Mezgebu Dagnachew, Hwee Ying Lim, Liao Wupeng, Sheau Yng Lim, Lim Sheng Jie Natalie, Veronique Angeli

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Collagen is essential for maintaining lung structure and function, and its remodeling has been associated with respiratory diseases, including chronic obstructive pulmonary disease (COPD). However, the cellular mechanisms driving collagen remodeling and the functional implications of this process in the pathophysiology of pulmonary diseases remain poorly understood. Using a mouse model of Lyve-1 expressing macrophage depletion, we found that the absence of this subpopulation of tissue-resident macrophage led to the preferential deposition of type I collagen fibers around the alveoli and bronchi in the steady state. Further analysis by polarized light microscopy revealed that the collagen fibers accumulating in the lungs depleted of Lyve-1+ macrophages were thicker and crosslinked. A decrease in MMP-9 gene expression and proteolytic activity, together with an increase in Col1a1, Timp-3 and Lox gene expression, accompanied the collagen alterations. Next, we investigated the effect of the collagen remodeling on the pathophysiology of COPD and airway function in mouse lacking Lyve-1+ macrophage exposed chronically to cigarette smoke (CS), a well-established animal model of COPD. We showed that the deposition of collagen protected mouse against the destruction of alveoli (emphysema) and bronchi thickening after CS exposure and prevented loss of airway function. Thus, we demonstrate that interstitial Lyve-1+ macrophages regulate the composition, amount, and architecture of the collagen network in the lungs and that such collagen remodeling functionally impacts the development of COPD. This study further supports the potential of targeting collagen as a promising approach to treating respiratory diseases.

Keywords: lung, extracellular matrix, chronic obstructive pulmonary disease, matrix metalloproteinases, collagen

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Authors: Itsuo Yokoyama, Rikako Kikuti, Miti Sekikawa, Tosinori Asai, Sarai Tsuyoshi

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Introduction: Vascular access for hemodialysis therapy is often difficult, even for experienced medical personnel. Ultrasound guided needle placement have been performed occasionally but is not always helpful in certain cases with complicated vascular anatomy. Obtaining precise anatomical knowledge of the vascular structure is important to prevent access-related complications. With augmented reality (AR) device such as AR glasses, the virtual vascular structure is shown superimposed on the actual patient vessels, thus enabling the operator to maneuver catheter placement easily with free both hands. We herein report our method of AR guided vascular access method in dialysis treatment Methods: Three dimensional (3D) object of the arm with arteriovenous fistula is computer graphically created with 3D software from the data obtained by computer tomography, ultrasound echogram, and image scanner. The 3D vascular object thus created is viewed on the screen of the AR digital display device (such as AR glass or iPad). The picture of the vascular anatomical structure becomes visible, which is superimposed over the real patient’s arm, thereby the needle insertion be performed under the guidance of AR visualization with ease. By this method, technical difficulty in catheter placement for dialysis can be lessened and performed safely. Considerations: Virtual reality technology has been applied in various fields and medical use is not an exception. Yet AR devices have not been widely used among medical professions. Visualization of the virtual vascular object can be achieved by creation of accurate three dimensional object with the help of computer graphical technique. Although our experience is limited, this method is applicable with relative easiness and our accumulating evidence has suggested that our method of vascular access with the use of AR can be promising.

Keywords: abdominal-aorta, calcification, extraskeletal, dialysis, computer graphics, 3DCG, CT, calcium, phosphorus

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Authors: Mahsa Hadipour Jahromy, Sara Rezaii

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Parkinson’s disease (PD) results primarily from the death of dopaminergic neurons in the substantia nigra. Soon after the discovery of levodopa and its beneficial effects in chronic administration, debilitating involuntary movements observed, termed levodopa-induced dyskinesia (LID) with poorly understood pathogenesis. Polyphenol-rich compounds, like pomegranate, provided neuroprotection in several animal models of brain diseases. In the present work, we investigated whether pomegranate has preventive effects following 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic degenerations and the potential to diminish LID in mice. Mice model of PD was induced by MPTP (30 mg/kg daily for five consecutive days). To induce a mice model of LID, valid PD mice were treated with levodopa (50 mg/kg, i.p) for 15 days. Then the effects of chronic co-administration of pomegranate juice (20 ml/kg) with levodopa and continuing for 10 days, evaluated. Behavioural tests were performed in all groups, every other day including: Abnormal involuntary movements (AIMS), forelimb adjusting steps, cylinder, and catatonia tests. Finally, brain tissue sections were prepared to study substantia nigra changes and dopamine neuron density after treatments. With this MPTP regimen, significant movement disorders revealed in AIMS tests and there was a reduction in dopamine striatal density. Levodopa attenuates their loss caused by MPTP, however, in chronic administration, dyskinesia observed in forelimb adjusting step and cylinder tests. Besides, catatonia observed in some cases. Chronic pomegranate co-administration significantly improved LID in both tests and reduced dopaminergic loss in substantia nigra. These data indicate that pomegranate might be a good adjunct for preserving dopaminergic neurons in the substantia nigra and reducing LID in mice.

Keywords: levodopa-induced dyskinesia, MPTP, Parkinson’s disease, pomegranate

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Authors: Sylwia Orzechowska, Andrzej Wróbel, Eugeniusz Rokita

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The mineralization is a curious problem of connective tissues. Factors which may play a decisive role in the regulation of the yellow ligaments (YL) mineralization are still open questions. The aim of the studies was a detailed description of the chemical composition and morphology of mineral deposits in the human yellow ligaments. Investigations of the structural features of deposits were used to explain the impact of various factors on mineralization process. The studies were carried out on 24 YL samples, surgically removed from patients suffer from spinal canal stenosis and the patients who sustained a trauma. The micro-computed tomography was used to describe the morphology of mineral deposits. The X-ray fluorescence method and Fourier transform infrared spectroscopy were applied to determine the chemical composition of the samples. In order to eliminate the effect of blur in microtomographic images, the correction method of partial volume effect was used. The mineral deposits appear in 60% of YL samples, both in patients with a stenosis and following injury. The mineral deposits have a heterogeneous structure and they are a mixture of the tissue and mineral grains. The volume of mineral grains amounts to (1.9 ± 3.4)*10-3 mm3 while the density distribution of grains occurs in two distinct ranges (1.75 - 2.15 and 2.15-2.5) g/cm3. Application of the partial volume effect correction allows accurate calculations by eliminating the averaging effect of gray levels in tomographic images. The B-type carbonate-containing hydroxyapatite constitutes the mineral phase of majority YLs. The main phase of two samples was calcium pyrophosphate dihydrate (CPPD). The elemental composition of minerals in all samples is almost identical. This pathology may be independent on the spine diseases and it does not evoke canal stenosis. The two ranges of grains density indicate two stages of grains growth and the degree of maturity. The presence of CPPD crystals may coexist with other pathologies.

Keywords: FTIR, micro-tomography, mineralization, spinal ligaments

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Authors: Nadine Wiesmann, Melanie Viel, Christoph Buhr, Rachel Tanner, Wolfgang Tremel, Juergen Brieger

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Recidivation of tumors and the development of resistances against the classical anti-tumor approaches represent a major challenge we face when treating cancer. In order to master this challenge, we are in desperate need of new treatment options beyond the beaten tracks. Zinc oxide nanoparticles (ZnO NPs) represent such an innovative approach. Zinc oxide is characterized by a high level of biocompatibility, concurrently ZnO NPs are able to exert anti-tumor effects. By concentration of the nanoparticles at the tumor site, tumor cells can specifically be exposed to the nanoparticles while low zinc concentrations at off-target sites are tolerated well and can be excreted easily. We evaluated the toxicity of ZnO NPs in vitro with the help of immortalized tumor cell lines and primary cells stemming from healthy tissue. Additionally, the Chorioallantoic Membrane Assay (CAM Assay) was employed to gain insights into the in vivo behavior of the nanoparticles. We could show that ZnO NPs interact with tumor cells as nanoparticulate matter. Furthermore, the extensive release of zinc ions from the nanoparticles nearby and within the tumor cells results in overload with zinc. Beyond that, ZnO NPs were found to further the generation of reactive oxygen species (ROS). We were able to show that tumor cells were more prone to the toxic effects of ZnO NPs at intermediate concentrations compared to fibroblasts. With the help of ZnO NPs covered by a silica shell in which FITC dye was incorporated, we were able to track ZnO NPs within tumor cells as well as within a whole organism in the CAM assay after injection into the bloodstream. Depending on the applied concentrations, selective tumor cell killing seems feasible. Furthermore, the combinational treatment of tumor cells with radiotherapy and ZnO NPs shows promising results. Still, further investigations are needed to gain a better understanding of the interaction between ZnO NPs and the human body to be able to pave the way for their application as an innovative anti-tumor agent in the clinics.

Keywords: metal oxide nanoparticles, nanomedicine, overcome resistances against classical treatment options, zinc oxide nanoparticles

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Authors: Mohamed Abdel-Hamid, Olfat Gamil Shaker, Doha El-Sayed Ellakwa, Eman Fathy Abdel-Maksoud

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Introduction: Despite advances in the knowledge of the molecular virology of hepatitis C virus (HCV), the mechanisms of hepatocellular injury in HCV infection are not completely understood. Hepatitis C viral infection (HCV) influences the susceptibility to apoptosis. This could lead to insufficient antiviral immune response and persistent viral infection. Aim of this study: was to examine whether BCL-2 gene polymorphism at codon 43 (+127G/A or Ala43Thr) has an impact on development of hepatocellular carcinoma caused by chronic hepatitis C Egyptian patients. Subjects and Methods: The study included three groups; group 1: composing of 30 patients with hepatocellular carcinoma (HCC), group 2 composing of 30 patients with HCV, group 3 composing of 30 healthy subjects matching the same age and socioeconomic status were taken as a control group. Gene polymorphism of BCL2 (Ala43Thr) were evaluated by PCR-RFLP technique and measured for all patients and controls. Results: The summed 43Thr genotype was more frequent and statistically significant in HCC patients as compared to control group. This genotype of BCL2 gene may inhibit the programmed cell death which leads to disturbance in tissue and cells homeostasis and reduction in immune regulation. This result leads to viral replication and HCV persistence. Moreover, virus produces variety of mechanisms to block genes participated in apoptosis. This mechanism proves that HCV patients who have 43Thr genotype are more susceptible to HCC. Conclusion: The data suggest for the first time that the BCL2 polymorphism is associated with the susceptibility to HCC in Egyptian populations and might be used as molecular markers for evaluating HCC risk. This study clearly demonstrated that Chronic HCV exhibit a deregulation of apoptosis with the disease progression. This provides an insight into the pathogenesis of chronic HCV infection, and may contribute to the therapy.

Keywords: BCL2 gene, Hepatitis C Virus, Hepatocellular carcinoma, sensitivity, specificity, apoptosis

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Authors: Hichem Sebai, Mohamed Amine Jabri, Kais Rtibi, Haifa Tounsi, Lamjed Marzouki

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Artemisia campestris has been widely used in Tunisian traditional medicine for its health beneficial effects. However, the present study aims at evaluating the antiulcer effects of Artemisia campestris aqueous extract (ACAE) as well as the mechanism of action involved in such gastroprotection. In this respect, male Wistar rats were divided into seven groups: control, aspirin (ASPR), ASPR + various doses of ACAE (100, 200 and 400 mg/kg, b.w.), ASPR+ famotidine and ASPR+ caffeic acid. Animals were pre-treated with ACAE extract during 10 days. We firstly showed that aspirin administration was accompanied by an oxidative stress status assessed by an increase of malondialdehyde (MDA) level, a decrease of sulfhydryl -(SH) groups content and depletion of antioxidant enzyme activities such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Pre-treatment with ACAE protected against aspirin-induced gastric oxidative stress. More importantly, aspirin administration increased plasma and tissue hydrogen peroxide (H₂O₂), free iron and calcium levels while the ACAE pre-treatment reversed all aspirin-induced intracellular mediators disturbance. The results of the present study clearly indicated that AEAC gastroprotection might be related, at least in part, to its antioxidant properties as well as to various gastric mucosal defense mechanisms, including the protection of gastric sulfhydryls and an opposite effect on some intracellular mediators such as free iron, hydrogen peroxide, and calcium. However, our data confirm the use of Artemisia campestris extracts in the Tunisian traditional folk medicine for the treatment of gastrointestinal diseases.

Keywords: gastric ulcer, Artemisia campestris, oxidative stress, sulfhydryl groups, Fenton reaction, rat

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

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

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

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Authors: Clotilde Guyon, Nada Jmari, Yen-Chin Li, Jean Denoyel, Noriyuki Fujikado, Christophe Blanchet, David Root, Matthieu Giraud

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Aire induces ectopic expression of a large repertoire of tissue-specific antigen (TSA) genes in thymic medullary epithelial cells (MECs), driving immunological self-tolerance in maturing T cells. Although important mechanisms of Aire-induced transcription have recently been disclosed through the identification and the study of Aire’s partners, the fine transcriptional functions underlied by a number of them and conferred to Aire are still unknown. Alternative cleavage and polyadenylation (APA) is an essential mRNA processing step regulated by the termination complex consisting of 85 proteins, 10 of them have been related to Aire. We evaluated APA in MECs in vivo by microarray analysis with mRNA-spanning probes and RNA deep sequencing. We uncovered the preference of Aire-dependent transcripts for short-3’UTR isoforms and for proximal poly(A) site selection marked by the increased binding of the cleavage factor Cstf-64. RNA interference of the 10 Aire-related proteins revealed that Clp1, a member of the core termination complex, exerts a profound effect on short 3’UTR isoform preference. Clp1 is also significantly upregulated in the MECs compared to 25 mouse tissues in which we found that TSA expression is associated with longer 3’UTR isoforms. Aire-dependent transcripts escape a global 3’UTR lengthening associated with MEC differentiation, thereby potentiating the repressive effect of microRNAs that are globally upregulated in mature MECs. Consistent with these findings, RNA deep sequencing of actinomycinD-treated MECs revealed the increased stability of short 3’UTR Aire-induced transcripts, resulting in TSA transcripts accumulation and contributing for their enrichment in the MECs.

Keywords: Aire, central tolerance, miRNAs, transcription termination

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Authors: Hany M. Fayed, Rehab F. Abdel-Rahman, Alyaa F. Hessin, Hanan A. Ogaly, Gihan F. Asaad, Abeer A. A. Salama, Sahar Abdelrahman, Mahmoud S. Arbid, Marwan Abd Elbaset Mohamed

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Liver fibrosis is a serious global health problem that occurs as a result of a variety of chronic liver disorders. Apigenin, a flavonoid found in many plants, has several pharmacological properties. The aim of this study was to evaluate the antifibrotic efficacy of apigenin (APG) against experimentally induced hepatic fibrosis in rats via using thioacetamide (TAA) and to explore the possible underlying mechanisms. TAA (100 mg/kg, i.p.) was given three times each week for two weeks to induce liver fibrosis. After TAA injections, APG was given orally (5 and 10 mg/kg) daily for two weeks. Biochemical, molecular, histological and immunohistochemical analyses were performed on blood and liver tissue samples. The functioning of the liver, oxidative stress, inflammation, and liver fibrosis indicators were all evaluated. The findings showed that TAA markedly increased the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as well as the levels of malondialdehyde (MDA), focal adhesion kinase (FAK), hypoxia-inducible factor-1 (HIF-1), nuclear factor-κB (NF-κB), transforming growth factor-beta (TGF-β), tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) with a reduction in albumin, total protein, A/G ratio, GSH content and interleukin-10 (IL-10). Moreover, TAA elevated the content of collagen I, α -smooth muscle actin (α-SMA), and hydroxyproline in the liver. The treatment with APG in a dose-dependent manner has obviously prevented these alterations and amended the harmful effects induced by TAA. The histopathological and immunohistochemical observations supported this biochemical evidence. The higher dose of APG produced the most significant antifibrotic effect. As a result of these data, APG appears to be a promising antifibrotic drug and could be used as a new herbal medication or dietary supplement in the future for the treatment of liver fibrosis. This effect might be related to the inhibition of the HIF-1/FAK signaling pathway.

Keywords: apigenin, FAK, HIF-1, liver fibrosis, rat, thioacetamide

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