Standardized GMP-Compliant Scalable 3D-Bioprocessing of Epidermal Stem Cells for Diabetic Foot Ulcers.

Diabetic foot ulcers (DFUs) pose a significant threat to the health and well-being of individuals with diabetes, often leading to lower limb amputations. Fortunately, epidermal stem cell therapy offers hope for improving the treatment of DFUs. By leveraging 3D culture techniques, the scalability of stem cell manufacturing can be greatly enhanced. In particular, using bioactive materials and scaffolds can promote the healing potential of cells, enhance their proliferation, and facilitate their survival. Furthermore, 3D tissue-mimicking cultures can accurately replicate the complex interactions between cells and extracellular matrix, thereby ensuring that the stem cells are primed for therapeutic application. To ensure the safety and quality of these stem cells, it is essential to adhere to good manufacturing practice (GMP) principles during cultivation. This chapter provides a comprehensive overview of the step-by-step process for GMP-based 3D epidermal stem cell cultivation, thus laying the groundwork for developing reliable regenerative medicine therapies.

The wonders of stem cells therapeutic application towards chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a respiratory condition characterized by its heterogeneous nature, progressive course, and significant impact on individuals' quality of life. It is a prevalent global health issue affecting a substantial number of individuals and can pose life-threatening complications if left unmanaged. The development and course of COPD can be influenced by a range of risk factors, including genetic predisposition and environmental exposures. Nevertheless, as researchers adopt a more comprehensive and expansive viewpoint of therapeutic techniques, the associated obstacles become more apparent. Indeed, a definitive medication for COPD that reliably leads to symptom alleviation has not yet been discovered. Therefore, the limitations of conventional therapy methods prompted researchers to focus on the advancement of novel procedures, potentially leading to significant outcomes. In contemporary times, the field of regenerative medicine and cell therapy has presented unprecedented opportunities for the exploration of innovative treatments for COPD, owing to the distinctive attributes exhibited by stem cells. Hence, it is imperative to provide due consideration to preclinical investigations and notable characteristics of stem cells as they serve as a means to comprehensively comprehend the fundamental mechanisms of COPD and uncover novel therapeutic strategies with enhanced efficacy for patients.

Association of plasma acylcarnitines and amino acids with hypertension: A nationwide metabolomics study.

BACKGROUND: Identification of metabolomics profile in subjects with different blood pressure, including normal blood pressure, elevated blood pressure, stage 1 hypertension, and stage 2 hypertension, would be a promising strategy to understand the pathogenesis of hypertension. Thus, we conducted this study to investigate the association of plasma acylcarnitines and amino acids with hypertension in a large Iranian population. METHODS: 1200 randomly selected subjects from the national survey on the Surveillance of Risk Factors of Non-Communicable Diseases in Iran (STEPs 2016) were divided into four groups based on the ACC/AHA hypertension criteria: normal blood pressure (n = 293), elevated blood pressure (n = 135), stage 1 hypertension (n = 325), and stage 2 hypertension (n = 447). Plasma concentrations of 30 acylcarnitines and 20 amino acids were measured using a targeted approach with flow-injection tandem mass spectrometry. Univariate and multivariate logistic regression analysis was applied to estimate the association between metabolites level and the risk of hypertension. Age, sex, BMI, total cholesterol, triglyceride, HDL cholesterol, fasting plasma glucose, use of oral glucose-lowering drugs, statins, and antihypertensive drugs were adjusted in regression analysis. RESULTS: Of 50 metabolites, 34 were associated with an increased likelihood of stage 2 hypertension and 5 with a decreased likelihood of stage 2 hypertension. After full adjustment for potential confounders, 5 metabolites were still significant risk markers for stage 2 hypertension including C0 (OR = 0.75; 95%CI: 0.63, 0.90), C12 (OR = 1.18; 95%CI: 1.00, 1.40), C14:1 (OR = 1.20; 95%CI: 1.01, 1.42), C14:2 (OR = 1.19; 95%CI: 1.01, 1.41), and glycine (OR = 0.81; 95%CI: 0.68, 0.96). An index that included glycine and serine also showed significant predictive value for stage 2 hypertension after full adjustment (OR = 0.86; 95%CI: 0.75, 0.98). CONCLUSIONS: Five metabolites were identified as potentially valuable predictors of stage 2 hypertension.

Advancement of Organoid Technology in Regenerative Medicine.

Purpose: Organoids are three-dimensional cultures of stem cells in an environment similar to the body's extracellular matrix. This is also a novel development in the realm of regenerative medicine. Stem cells can begin to develop into 3D structures by modifying signaling pathways. To form organoids, stem cells are transplanted into the extracellular matrix. Organoids have provided the required technologies to reproduce human tissues. As a result, it might be used in place of animal models in scientific study. The key goals of these investigations are research into viral and genetic illnesses, malignancies, and extracellular vesicles, pharmaceutical discovery, and organ transplantation. Organoids can help pave the road for precision medicine through genetic editing, pharmaceutical development, and cell therapy. Methods: PubMed, Google Scholar, and Scopus were used to search for all relevant papers written in English (1907-2021). The study abstracts were scrutinized. Studies on the use of stem-cell-derived organoids in regenerative medicine, organoids as 3D culture models for EVs analysis, and organoids for precision medicine were included. Articles with other irrelevant aims, meetings, letters, commentaries, congress and conference abstracts, and articles with no available full texts were excluded. Results: According to the included studies, organoids have various origins, types, and applications in regenerative and precision medicine, as well as an important role in studying extracellular vesicles. Conclusion: Organoids are considered a bridge that connects preclinical studies to clinical ones. However, the lack of a standardized protocol and other barriers addressed in this review, hinder the vast use of this technology. Lay Summary: Organoids are 3D stem cell propagations in biological or synthetic scaffolds that mimic ECM to allow intercellular or matrix-cellular crosstalk. Because these structures are similar to organs in the body, they can be used as research models. Organoids are medicine's future hope for organ transplantation, tumor biobank formation, and the development of precision medicine. Organoid models can be used to study cell-to-cell interactions as well as effective factors like inflammation and aging. Bioengineering technologies are also used to define the size, shape, and composition of organoids before transforming them into precise structures. Finally, the importance of organoid applications in regenerative medicine has opened a new window for a better understanding of biological research, as discussed in this study.

Docking study, molecular dynamic, synthesis, anti-α-glucosidase assessment, and ADMET prediction of new benzimidazole-Schiff base derivatives.

The control of postprandial hyperglycemia is an important target in the treatment of type 2 diabetes mellitus (T2DM). As a result, targeting α-glucosidase as the most important enzyme in the breakdown of carbohydrates to glucose that leads to an increase in postprandial hyperglycemia is one of the treatment processes of T2DM. In the present work, a new class of benzimidazole-Schiff base hybrids 8a-p has been developed based on the potent reported α-glucosidase inhibitors. These compounds were synthesized by sample recantations, characterized by 1H-NMR, 13C-NMR, FT-IR, and CHNS elemental analysis, and evaluated against α-glucosidase. All new compounds, with the exception of inactive compound 8g, showed excellent inhibitory activities (60.1 ± 3.6-287.1 ± 7.4 µM) in comparison to acarbose as the positive control (750.0 ± 10.5). Kinetic study of the most potent compound 8p showed a competitive type of inhibition (Ki value = 60 µM). In silico induced fit docking and molecular dynamics studies were performed to further investigate the interaction, orientation, and conformation of the title new compounds over the active site of α-glucosidase. In silico druglikeness analysis and ADMET prediction of the most potent compounds demonstrated that these compounds were druglikeness and had satisfactory ADMET profile.

Self-perceived health and functional status of older people: Telephone-based lifestyle survey of older adults in Tehran province.

Background: The prevalence study of health conditions can help policy makers to document base policymaking. This study aimed to reveal the health status, including the prevalence of geriatric syndrome health conditions such as activity of daily livings, pain, and physical and mental health of older adults in Tehran province. Methods: This cross-sectional study was a telephone survey with older people ≥60 years old using a systematic random sampling of telephone numbers in Tehran province. The Persian version of the Katz' activity of daily living (ADL) and the Lawton's instrumental activity of daily living (IADL) questionnaires were used to evaluate the functional status. Pain, history of chronic diseases, continence, hospital admission, sensory problems, and self-perceived health (SPH) were asked by trained nurses or gerontologists thorough telephone interviews. Results: In this study, 1251 older adults with the mean age of 67.03±7.51 years have been recruited. About 64.50% (95% CI: 64.4-64.6) of them were totally independent according to ADL (female=60.02% and male=68.50%), and about 40.50% (95% CI: 40.4-40.5) were independent based on IADL domains (female=39.41% and male=41.80). The dependency rates in ADL increased with the aging of population. Joint pain was the most prevalent type of pains and near to 26.00% (95% CI: 64.4-64.6) of the participants suffered moderate joint pains. About 71.5% (95% CI: 71.4-71.5) of the participants were urinary continent (female=67.66% and male=76.06%), and 91.9% (95% CI: 91.9-92.0) had bowel control (female=91.47% and male=92.94%) and the prevalence of incontinence increased by advancing age. Only 26.70% (95% CI: 26.6-26.8) of the participants reported excellent and good levels of perceived health status (female=21.98% and male=31.48%) and about 26.2% (95% CI: 26.1-26.2) of them reported some degree of visual impairment. Conclusion: The results of the present study can provide a good view about the health profile of older adults, including pain, functional status, sphincter control, chronic diseases, sensory status, and SPH. Future studies should prioritize SPH as an important predictor of mortality rates.

The Fingerprints of Biomedical Science in Internal Medicine.

With the development of numerous advances in science and technologies, medical science has also been updated. Internal medicine is one of the most valuable specialized fields of medical sciences that review a broad range of diseases. Herein, the internal medicine specialist (internist) is obliged to do diagnostic measures to evaluate disease signs and symptoms. In recent times, biomedical sciences as the new emergence science (including cellular and molecular biology, genetics, nanobiotechnology, bioinformatics, biochemistry, etc.) have been capable of providing more specific diagnostic methods together with techniques for better understanding the mechanism of the disease and the best diseases modeling and offering proper therapies. Accordingly, the authors have tried to review the link between biomedical sciences and medicine, particularly internal medicine.

Diabetic foot workshop: A strategy for improving the knowledge of diabetic foot care providers.

BACKGROUND AND AIMS: Prevention and management of diabetic foot ulcer have essential effects on the quality of life of patients. Accordingly training the care providers can play an essential role in reducing complications foot ulcers and lead to an increase in the effectiveness and efficiency of patient health cares. We conducted a study to survey the impact of the diabetic foot workshop on the knowledge of nurses and physicians about diagnosis and managing diabetic foot. METHODS: The present study is a quasi-experimental which compare the knowledge of non-randomized group of nurses and physicians about diabetic foot care. The leaning objectives, agenda, contents and evaluation methods of the diabetic foot care workshop was designed by a multidisciplinary team members in form of 2 days workshop. Each topic of the workshop presented theoretically and practically using educational cases and real patient with diabetic foot ulcer. A valid and reliable questionnaire with 20 Multiple Choice Questions used for the evaluation of workshopin form of the pretest and posttest. RESULTS: In this study, 396 registered nurses and physicians participates in the diabetic foot workshop series. The results of this study showed that this increase in the level of knowledge was meaningful after the educational intervention since the mean of the posttest score increased more than 20% comparing with pretest. CONCLUSION: The promotion of knowledge of health care providers as shown in the study may almost be due to training by real patient, team-working, and using educational movies for the education of diabetic foot diagnosis, management and rehabilitation.

New 4-phenylpiperazine-carbodithioate-N-phenylacetamide hybrids: Synthesis, in vitro and in silico evaluations against cholinesterase and α-glucosidase enzymes.

A series of novel 4-phenylpiperazine-carbodithioate-N-phenylacetamide hybrids (6a-n) was designed, synthesized, and evaluated for their in vitro inhibitory activity against the metabolic enzymes, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α-glucosidase. The obtained results showed that most of the synthesized compounds exhibited high to good anti-AChE and anti-BChE activity in the range of nanomolar concentrations in comparison to tacrine as a positive control. Molecular modeling of the most potent compounds 6e and 6i demonstrated that these compounds interacted with important residues of the AChE and BChE active sites. Moreover, all the newly synthesized compounds 6a-n had significant Ki values against α-glucosidase when compared with the positive control acarbose. Representatively, N-2-fluorophenylacetamide derivative 6l, with a Ki value of 0.98 nM as the most potent compound, was 126 times more potent than acarbose with a Ki value of 123.70 nM. This compound also fitted in the α-glucosidase active site and interacted with key residues. An in silico study of the druglikeness/absorption, distribution, metabolism, and excretion (ADME)/toxicity profile of the selected compounds 6e, 6i, and 6l predicts that these compounds are drug-like and have the appropriate properties in terms of ADME and toxicity.

Machine Learning: A New Prospect in Multi-Omics Data Analysis of Cancer.

Cancer is defined as a large group of diseases that is associated with abnormal cell growth, uncontrollable cell division, and may tend to impinge on other tissues of the body by different mechanisms through metastasis. What makes cancer so important is that the cancer incidence rate is growing worldwide which can have major health, economic, and even social impacts on both patients and the governments. Thereby, the early cancer prognosis, diagnosis, and treatment can play a crucial role at the front line of combating cancer. The onset and progression of cancer can occur under the influence of complicated mechanisms and some alterations in the level of genome, proteome, transcriptome, metabolome etc. Consequently, the advent of omics science and its broad research branches (such as genomics, proteomics, transcriptomics, metabolomics, and so forth) as revolutionary biological approaches have opened new doors to the comprehensive perception of the cancer landscape. Due to the complexities of the formation and development of cancer, the study of mechanisms underlying cancer has gone beyond just one field of the omics arena. Therefore, making a connection between the resultant data from different branches of omics science and examining them in a multi-omics field can pave the way for facilitating the discovery of novel prognostic, diagnostic, and therapeutic approaches. As the volume and complexity of data from the omics studies in cancer are increasing dramatically, the use of leading-edge technologies such as machine learning can have a promising role in the assessments of cancer research resultant data. Machine learning is categorized as a subset of artificial intelligence which aims to data parsing, classification, and data pattern identification by applying statistical methods and algorithms. This acquired knowledge subsequently allows computers to learn and improve accurate predictions through experiences from data processing. In this context, the application of machine learning, as a novel computational technology offers new opportunities for achieving in-depth knowledge of cancer by analysis of resultant data from multi-omics studies. Therefore, it can be concluded that the use of artificial intelligence technologies such as machine learning can have revolutionary roles in the fight against cancer.

Potential for Stem Cell-Based Therapy in the Road of Treatment for Neurological Disorders Secondary to COVID-19.

Abstract: The severe acute respiratory syndrome coronavirus 2 has led to the worldwide pandemic named coronavirus disease 2019 (COVID-19). It has caused a significant increase in the number of cases and mortalities since its first diagnosis in December 2019. Although COVID-19 primarily affects the respiratory system, neurological involvement of the central and peripheral nervous system has been also reported. Herein, the higher risk of neurodegenerative diseases in COVID-19 patients in future is also imaginable. Neurological complications of COVID-19 infection are more commonly seen in severely ill individuals; but, earlier diagnosis and treatment can lead to better long-lasting results. In this respect, stem cell biotechnologies with considerable self-renewal and differentiation capacities have experienced great progress in the field of neurological disorders whether in finding out their underlying processes or proving them promising therapeutic approaches. Herein, many neurological disorders have been found to benefit from stem cell medicine strategies. Accordingly, in the present review, the authors are trying to discuss stem cell-based biotechnologies as promising therapeutic options for neurological disorders secondary to COVID-19 infection through reviewing neurological manifestations of COVID-19 and current stem cell-based biotechnologies for neurological disorders. Lay Summary: Due to the substantial burden of neurological disorders in the health, economic, and social system of society, the emergence of neurological manifestations following COVID-19 (as a life-threatening pandemic) creates the need to use efficient and modern methods of treatment. Since stem cell-based methods have been efficient for a large number of neurological diseases, it seems that the use of mentioned methods is also effective in the process of improving neurological disorders caused by COVID-19. Hereupon, the current review aims to address stem cell-based approaches as treatments showing promise to neurological disorders related to COVID-19.

Recent Advances of COVID-19 Modeling Based on Regenerative Medicine.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has caused a pandemic since December 2019 that originated in Wuhan, China. Soon after that, the world health organization declared Coronavirus disease-2019 a global health concern. SARS-CoV-2 is responsible for a lethal respiratory infection as well as the involvement of other organs due to its large tropism spectrum such as neurologic, cardiovascular, endocrine, gastrointestinal, and renal systems. Since the behavior of the virus is not fully understood, a new manifestation of the infection is revealed every day. In order to be able to design more efficient drugs and vaccines to treat the infection, finding out the exact mechanism of pathogenicity would be necessary. Although there have been some big steps toward understanding the relevant process, there are still some deficiencies in this field. Accordingly, regenerative medicine (RM), can offer promising opportunities in discovering the exact mechanisms and specific treatments. For instance, since it is not always possible to catch the pathophysiology mechanisms in human beings, several modeling methods have been introduced in this field that can be studied in three main groups: stem cell-based models, organoids, and animal models. Regarding stem cell-based models, induced pluripotent stem cells are the major study subjects, which are generated by reprogramming the somatic stem cells and then directing them into different adult cell populations to study their behavior toward the infection. In organoid models, different cell lines can be guided to produce a 3D structure including liver, heart, and brain-like platforms. Among animal models, mice are the most common species in this field. However, in order for mice models to be permissive to the virus, angiotensin-converting enzyme 2 receptors, the main receptor involved in the pathogenicity of the virus, should be introduced to the host cells through different methods. Here, the current known mechanism of SARS-CoV-2 infection, different suggested models, the specific response toward different manipulation as well as challenges and shortcomings in each case have been reviewed. Finally, we have tried to provide a quick summary of the present available RM-based models for SARS-CoV-2 infection, as an essential part of developing drugs, for future therapeutic goals.

Integration Experiences of Former Afghan Refugees in Australia: What Challenges Still Remain after Becoming Citizens?

This paper explores, analyses, and documents the experiences of Afghan-Australians who arrived in Australia as refugees and were granted citizenship after living in Australia for several years. This research adopted a mixed method of qualitative and quantitative approaches and surveyed 102 people, interviewed 13 participants, and conducted two focus-groups within its research design. Analysis of data indicates that former Afghan refugees gradually settled down and integrated within Australian society. They value safety and security, open democracy and orderly society of Australia, as well as accessing to education and healthcare services and opportunity for social mobility. However, since the integration is a long process, they are also facing some challenges in this area. Findings of this study show that Afghan-Australians require more support from Australian governments to overcome some of these challenges particularly securing employment within their area of interests and professional occupations that they have qualifications and experiences from Afghanistan. They are also experiencing broader challenges in the area of socio-cultural issues within Australian society. Since the Afghan community is an emerging community in Western Australia, they require more support from local government to enhance their ethnic cohesion and solidarity.

Empowering Health Care Providers and Self-management Education in Diabetes? A Scoping Review.

CONTEXT: There has been an increasing emphasis on the role of education in diabetes prevention and management, and shedding light on evidence gaps is mandatory for national action plans establishment. DATA SOURCES: This scoping review was part of the Iranian Diabetes Road Map project that used a systematic method based on the Arksey and O'Malley approach. RESULTS: After the screening, 173 articles were included, most of which were published in 2018 and focused on self-management. Most included articles were considered patient-related self-management/care/efficacy, while only a limited number of articles studied healthcare provider education and educational establishment. Additionally, a significant number of included studies were addressed virtual education, an issue as the strength of Iranian studies in diabetes education. CONCLUSIONS: Education is an important part of diabetes, and specific needs for Iranian patients should be addressed in future studies. Paying attention to new topics and conducting high-quality interventional studies will help fill evidence gaps in this field in Iran.

COVID-19 Pathology on Various Organs and Regenerative Medicine and Stem Cell-Based Interventions.

Severe acute respiratory syndrome-coronavirus 2, a novel betacoronavirus, has caused the global outbreak of a contagious infection named coronavirus disease-2019. Severely ill subjects have shown higher levels of pro-inflammatory cytokines. Cytokine storm is the term that can be used for a systemic inflammation leading to the production of inflammatory cytokines and activation of immune cells. In coronavirus disease-2019 infection, a cytokine storm contributes to the mortality rate of the disease and can lead to multiple-organ dysfunction syndrome through auto-destructive responses of systemic inflammation. Direct effects of the severe acute respiratory syndrome associated with infection as well as hyperinflammatory reactions are in association with disease complications. Besides acute respiratory distress syndrome, functional impairments of the cardiovascular system, central nervous system, kidneys, liver, and several others can be mentioned as the possible consequences. In addition to the current therapeutic approaches for coronavirus disease-2019, which are mostly supportive, stem cell-based therapies have shown the capacity for controlling the inflammation and attenuating the cytokine storm. Therefore, after a brief review of novel coronavirus characteristics, this review aims to explain the effects of coronavirus disease-2019 cytokine storm on different organs of the human body. The roles of stem cell-based therapies on attenuating cytokine release syndrome are also stated.

Effects of supplementation with main coffee components including caffeine and/or chlorogenic acid on hepatic, metabolic, and inflammatory indices in patients with non-alcoholic fatty liver disease and type 2 diabetes: a randomized, double-blind, placebo-controlled, clinical trial.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is much more frequent and more severe, including cirrhosis, hepatocellular carcinoma in patients with type 2 diabetes. Coffee is a complex beverage with hundreds of compounds whereas caffeine and chlorogenic acid are the most abundant bioactive compounds. The published epidemiological data demonstrating beneficial associations between all categories of coffee exposure and ranges of liver outcomes are rapidly growing; however, the main contributors and cause-effect relationships have not yet been elucidated. To address existing knowledge gaps, we sought to determine the efficacy and safety of 6 months chlorogenic acid and/or caffeine supplementation in patients with type 2 diabetes affected by NAFLD. METHODS: This trial was carried out at two Diabetes Centers to assess the effects of supplementation with daily doses of 200 mg chlorogenic acid, 200 mg caffeine, 200 mg chlorogenic acid plus 200 mg caffeine or placebo (starch) in patients with type 2 diabetes and NAFLD. The primary endpoint was reduction of hepatic fat and stiffness measured by FibroScan, and changes in serum hepatic enzymes and cytokeratin - 18 (CK-18) levels. Secondary endpoints were improvements in metabolic (including fasting glucose, homeostasis model assessment-estimated insulin resistance (HOMA-IR), hemoglobin A1c (HBA1C), C-peptide, insulin and lipid profiles) and inflammatory (including nuclear factor k-B (NF-KB), tumor necrosis factor (TNF-α), high sensitive- C reactive protein(hs-CRP)) parameters from baseline to the end of treatment. RESULTS: Neither chlorogenic acid nor caffeine was superior to placebo in attenuation of the hepatic fat and stiffness and other hepatic outcomes in patients with diabetes and NAFLD. Except for the lower level of total cholesterol in caffeine group (p = 0.04), and higher level of insulin in chlorogenic acid plus caffeine group (p = 0.01) compared with placebo, there were no significant differences among the treatment groups. CONCLUSION: These findings do not recommend caffeine and/or chlorogenic acid to treat NAFLD in type 2 diabetes patients. TRIAL REGISTRATION: IRCT201707024010N21 . Registered 14 September 2017.

Human Fetal Skin Fibroblast Isolation and Expansion for Clinical Application.

Cell therapy is one of the most hopeful technologies of regenerative medicine approaches. Among various cells, human skin fibroblasts have been progressively used for wound healing as cell-based therapy purposes. By increasing the age, the number of skin fibroblasts' abilities including cell migration, growth, collagen production, etc. decreases. Hence, use of the fetal source is more beneficent. In this respect, this chapter covers the manufacturing of human fetal skin-derived fibroblasts for clinical application.

Molecular Characteristics of Methicillin-Resistant Staphylococcus aureus (MRSA) Isolated from Diabetic Foot Infection.

BACKGROUND & OBJECTIVE: Diabetic foot ulcer (DFU), is one of the most frequent causes for hospitalizations in patients with diabetes. A major problem in the treatment of DFU is the increased-incidence of methicillin-resistant Staphylococcus aureus (MRSA). The aim of this study was to determine the SCCmec types of MRSA isolates and their epidemiology among patients with diabetes. METHODS: This study was carried out on 145 diabetic patients with DFUs. The antibiotic susceptibility tests (ASTs) were performed using the disk diffusion method and E-test technique. SCCmec typing was done by multiplex PCR. Moreover, the presence of virulence toxin genes, including pvl and lukED was detected by PCR assay. RESULTS: In 145 samples from which S. aureus was predominantly isolated, 19.48% were MRSA. Analysis of MRSA isolates revealed that the most prevalent SCCmec type was type IV (46.7%) followed by type III (30.0%) and type V (20.0%). One strain (3.3%) was untypeable. The prevalence of pvl and lukED was 56.7% and 100%, respectively. CONCLUSION: The high prevalence of MRSA in DFUs represents the high levels of antibiotic usage among patients with diabetes. In this study, resistance to other important clinical antibiotics was detected among MRSA isolates. The high proportion of SCCmec type IV and V strains, even in former hospitalized patients, indicates the entrance of these clones to the clinical setting.

Development and validation of Alzheimer's Disease Animal Model for the Purpose of Regenerative Medicine.

One of the most common age-related neurodegenerative disorders is Alzheimer's disease which globally threatening the health of elderly people. Although there are several pharmacological and non- pharmacological treatments for Alzheimer's disease, they can just decrease the symptoms in these diseases. In this context, cell therapy and regenerative medicine approach as the novel therapeutic strategies for neurodegenerative diseases would be important. Based on scientific research principles, using any novel therapeutic approaches before the run in clinical trials need to take preclinical (animal study) stapes. Accordingly, an animal study can improve our understanding of biological mechanisms of diseases and as an important step should adhering to ethical guidelines and standards. On the other hand, to gain suitable outcomes, it is important to check the appropriate validation of animal models. In this regard, the present review would discuss about the development and validation of appropriate AD animal models in the field of regenerative medicine.