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BACKGROUND: The prevalence of Type 2 Diabetes Mellitus (T2DM) in the North Africa and Middle East region is alarmingly high, prompting us to investigate the burden and factors contributing to it through the GBD study. Additionally, there is a lack of knowledge about the epidemiological status of T2DM in this region, so our aim is to provide a comprehensive overview of the burden of T2DM and its associated risk factors. METHODS: Using data from the 2019 Global Burden of Disease Study, we calculated the attributable burden of T2DM for each of the 21 countries in the region for the years 1990 and 2019. This included prevalence, mortality, disability-adjusted life years (DALYs), and risk factors. RESULTS: Between 1990 and 2019, there was a significant increase in the age-standardized incidence (79.6%; 95% Uncertainty Interval: 75.0 to 84.5) and prevalence (85.5%; [80.8 to 90.3]) rates of T2DM per 100,000 populations. The age-standardized mortality rate (1.7%; [-10.4 to 14.9]), DALYs (31.2%; [18.3 to 42.2]), and years lived with disability (YLDs) (82.6%; [77.2 to 88.1]) also increased during this period. Modifiable risk factors, such as high body mass index (56.4%; [42.8 to 69.8]), low physical activity (15.5%; [9.0 to 22.8]), and ambient particulate matter pollution (20.9%; [15.2 to 26.2]), were the main contributors to the number of deaths. CONCLUSION: The burden of T2DM, in terms of mortality, DALYs, and YLDs, continues to rise in the region. The incidence rate of T2DM has increased in many areas. The burden of T2DM attributed to modifiable risk factors continues to grow in most countries. Targeting these modifiable risk factors could effectively reduce the growth and disease burden of T2DM in the region.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Carga Global da Doença , Fatores de Risco , África do Norte/epidemiologia , Oriente Médio/epidemiologiaRESUMO
Colorectal cancer is a global health concern with high incidence and mortality rates. Conventional treatments like surgery, chemotherapy, and radiation therapy have limitations in improving patient survival rates. Recent research highlights the role of gut microbiota and intestinal stem cells in maintaining intestinal health and their potential therapeutic applications in colorectal cancer treatment. The interaction between gut microbiota and stem cells influences epithelial self-renewal and overall intestinal homeostasis. Novel therapeutic approaches, including immunotherapy, targeted therapy, regenerative medicine using stem cells, and modulation of gut microbiota, are being explored to improve treatment outcomes. Accordingly, this chapter provides an overview of the potential therapeutic applications of gut microbiota and intestinal stem cells in treating colorectal cancer.
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Recent advancements in personalized treatments, such as anthracycline chemotherapy, coupled with timely diagnoses, have contributed to a decrease in cancer-specific mortality rates and an improvement in cancer prognosis. Anthracyclines, a potent class of antibiotics, are extensively used as anticancer medications to treat a broad spectrum of tumors. Despite these advancements, a considerable number of cancer survivors face increased risks of treatment complications, particularly the cardiotoxic effects of chemotherapeutic drugs like anthracyclines. These effects can range from subclinical manifestations to severe consequences such as irreversible heart failure and death, highlighting the need for effective management of chemotherapy side effects for improved cancer care outcomes. Given the lack of specific treatments, early detection of subclinical cardiac events post-anthracycline therapy and the implementation of preventive strategies are vital. An interdisciplinary approach involving cardiovascular teams is crucial for the prevention and efficient management of anthracycline-induced cardiotoxicity. Various factors, such as age, gender, duration of treatment, and comorbidities, should be considered significant risk factors for developing chemotherapy-related cardiotoxicity. Tools such as electrocardiography, echocardiography, nuclear imaging, magnetic resonance imaging, histopathologic evaluations, and serum biomarkers should be appropriately used for the early detection of anthracycline-related cardiotoxicity. Furthermore, understanding the underlying biological mechanisms is key to developing preventive measures and personalized treatment strategies to mitigate anthracycline-induced cardiotoxicity. Exploring specific cardiotoxic mechanisms and identifying genetic variations can offer fresh perspectives on innovative, personalized treatments. This chapter aims to discuss cardiomyopathy following anthracycline therapy, with a focus on molecular mechanisms, preventive strategies, and emerging treatments.
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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.
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Doença Pulmonar Obstrutiva Crônica , Qualidade de Vida , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Fatores de Risco , Células-TroncoRESUMO
Alzheimer's disease (AD), the most common type of senile dementia, is a chronic neurodegenerative disease characterized by cognitive dysfunction and behavioral disability. The two histopathological hallmarks in this disease are the extraneuronal accumulation of amyloid-ß (Aß) and the intraneuronal deposition of neurofibrillary tangles (NFTs). Despite this, central and peripheral metabolic dysfunction, such as abnormal brain signaling, insulin resistance, inflammation, and impaired glucose utilization, have been indicated to be correlated with AD. There is solid evidence that the age-associated thermoregulatory deficit induces diverse metabolic changes associated with AD development. Brown adipose tissue (BAT) has been known as a thermoregulatory organ particularly vital during infancy. However, in recent years, BAT has been accepted as an endocrine organ, being involved in various functions that prevent AD, such as regulating energy metabolism, secreting hormones, improving insulin sensitivity, and increasing glucose utilization in adult humans. This review focuses on the mechanisms of BAT activation and the effect of aging on BAT production and signaling. Specifically, the evidence demonstrating the effect of BAT on pathological mechanisms influencing the development of AD, including insulin pathway, thermoregulation, and other hormonal pathways, are reviewed in this article.
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Doença de Alzheimer , Resistência à Insulina , Doenças Neurodegenerativas , Humanos , Doença de Alzheimer/metabolismo , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/patologia , Peptídeos beta-Amiloides/metabolismo , Glucose/metabolismoRESUMO
Stem cells, as a group of undifferentiated cells, are enriched with self-renewal and high proliferative capacity, which have attracted the attention of many researchers as a promising approach in the treatment of many diseases over the past years. However, from the cellular and molecular point of view, the DNA repair system is one of the biggest challenges in achieving therapeutic goals through stem cell technology. DNA repair mechanisms are an advantage for stem cells that are constantly multiplying to deal with various types of DNA damage. However, this mechanism can be considered a trump card in the game of cell survival and treatment resistance in cancer stem cells, which can hinder the curability of various types of cancer. Therefore, getting a deep insight into the DNA repair system can bring researchers one step closer to achieving major therapeutic goals. The remarkable thing about the DNA repair system is that this system is not only under the control of genetic factors, but also under the control of epigenetic factors. Therefore, it is necessary to investigate the role of the DNA repair system in maintaining the survival of cancer stem cells from both aspects.
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Tissue engineering as an important field in regenerative medicine is a promising therapeutic approach to replace or regenerate injured tissues. It consists of three vital steps including the selection of suitable cells, formation of 3d scaffolds, and adding growth factors. Mesenchymal stem cells (MSCs) and embryonic stem cells (ESCs) are mentioned as two main sources for this approach that have been used for the treatment of various types of disorders. However, the main focus of literature in the field of dental tissue engineering is on utilizing MSCs. On the other hand, biocompatible scaffolds play a notable role in this regenerative process which is mentioned to be harmless with acceptable osteoinductivity. Their ability in inhibiting inflammatory responses also makes them powerful tools. Indeed, stem cell functions should be supported by biomaterials acting as scaffolds incorporated with biological signals. Naturally derived polymeric scaffolds and synthetically engineered polymeric/ceramic scaffolds are two main types of scaffolds regarding their materials that are defined further in this review. Various strategies of tissue bioengineering can affect the regeneration of dentin-pulp complex, periodontium regeneration, and whole teeth bioengineering. In this regard, in vivo/ex vivo experimental models have been developed recently in order to perform preclinical studies of dental tissue engineering which make it more transferable to be used for clinic uses. This review summarizes dental tissue engineering through its different components. Also, strategies of tissue bioengineering and experimental models are introduced in order to provide a perspective of the potential roles of dental tissue engineering to be used for clinical aims.
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Células-Tronco Mesenquimais , Engenharia Tecidual , Materiais Biocompatíveis/uso terapêutico , Medicina Regenerativa , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Embrionárias , Alicerces Teciduais , Polpa DentáriaRESUMO
Glioblastoma multiforme (GBM) is the most invasive form of primary brain astrocytoma, resulting in poor clinical outcomes. Herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) gene therapy is considered a promising strategy for GBM treatment. Since Connexin43 (Cx43) expression is reduced in GBM cells, increasing Cx43 levels could enhance the effectiveness of gene therapy. The present study aims to examine the impact of fluoxetine on HSV-TK/GCV gene therapy in human GBM cells using human olfactory ensheathing cells (OECs) as vectors. The effect of fluoxetine on Cx43 levels was assessed using the western blot technique. GBM-derived astrocytes and OECs-TK were Cocultured, and the effect of fluoxetine on the Antitumor effect of OEC-TK/GCV gene therapy was evaluated using MTT assay and flow cytometry. Our results showed that fluoxetine increased Cx43 levels in OECs and GBM cells and augmented the killing effect of OECs-TK on GBM cells. Western blot data revealed that fluoxetine enhanced the Bax/Bcl2 ratio and the levels of cleaved caspase-3 in the coculture of OECs-TK and GBM cells. Moreover, flow cytometry data indicated that fluoxetine increased the percentage of apoptotic cells in the coculture system. This study suggests that fluoxetine, by upregulating Cx43 levels, could strengthen the Antitumor effect of OEC-TK/GCV gene therapy on GBM cells.
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Ganciclovir , Glioblastoma , Humanos , Ganciclovir/farmacologia , Ganciclovir/uso terapêutico , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Conexina 43/genética , Conexina 43/metabolismo , Conexina 43/uso terapêutico , Timidina Quinase/genética , Timidina Quinase/metabolismo , Timidina Quinase/uso terapêutico , Fluoxetina/farmacologia , Fluoxetina/uso terapêutico , Regulação para Cima , Terapia Genética , Antivirais/farmacologiaRESUMO
The field of regenerative medicine (RM) as an innovative technology has the ability to affect the healthcare system. It develops a variety of techniques through stem cell biology, genetics, bioengineering, biomaterial science, and tissue engineering to replace or restore the role of lost, disabled, or aging cells in the human body. However, the field's proficiency has still been underwhelming at the clinical trial level. This could be due to the innovation of such technologies, as well as their incredible nature. Therefore, managing the infrastructure framework for the safe and efficient application of the aforementioned field of science would help in the process of progress. In this context, the current review focuses on how to establish infrastructures for more effective RM.
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Medicina Regenerativa , Engenharia Tecidual , Humanos , Medicina Regenerativa/métodos , Engenharia Tecidual/métodos , Materiais Biocompatíveis , Bioengenharia , Células-TroncoRESUMO
The severe acute respiratory syndrome coronavirus 2 has been a shocking disaster for healthcare systems worldwide since December 2019. This virus can affect all systems of the body and its symptoms vary from a simple upper respiratory infection to fatal complications including end-organ damage. On the other hand, the normal immune system plays a pivotal role in the recovery of infectious diseases such as COVID-19. However, occasionally, exaggerated immune system inflammation and an excessive synthesis of cytokines, known as a "cytokine storm," can deteriorate the patient's clinical condition. Secondary bacterial co-infection is another problem in COVID-19 which affects the prognosis of patients. Although there are a few studies about this complication, they suggest not using antibiotics commonly, especially broad-spectrum ones. During this pandemic, various approaches and therapeutics were introduced for treating COVID-19 patients. However, available treatments are not helpful enough, especially for complicated cases. Hence, in this era, cell therapy and regenerative medicine will create new opportunities. Therefore, the therapeutic benefits of mesenchymal stem cells, especially their antimicrobial activity, will help us understand how to treat COVID-19. Herein, mesenchymal stem cells may stop the immune system from becoming overactive in COVID-19 patients. On the other side, the stem cells' capacity for repair could encourage natural healing processes.
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Infecções Bacterianas , COVID-19 , Células-Tronco Mesenquimais , Humanos , Síndrome da Liberação de Citocina , SARS-CoV-2RESUMO
Background: Many elder people have knee osteoarthritis (OA). The patients are faced with pain and disability in movement. Given the challenging lifestyle of the patients, finding an efficient therapy approach is necessary. Since low-level laser therapy applies to the treatment of many diseases, it seems it can be a suitable option for the treatment of knee OA. The present study aimed to evaluate the molecular mechanism of laser therapy on knee OA via a protein expression change study. Methods: The present study examines the gene expression profile of patients with OA in the knee using bioinformatics. The protein expression change profile of synovial fluid of knee OA patients is extracted from the literature and is analyzed based on the rate of expression and interactions between the differentially expressed proteins (DEPs). The results are compared with the DEPs of similar tissue of the treated knee OA patients (from published documents) after laser therapy. Results: Apolipoprotein B (APOB) and matrix metallopeptidase 2 (MMP2) were determined as the hub bottlenecks of the protein-protein interaction (PPI) network of synovial fluid of knee OA patients. MMP2, complement 5, transthyretin, and apolipoprotein A-1 from laser-treated patients were related to the PPI network of knee OA patients. The reduction of Interleukin-6 activity was highlighted as a critical event as a function of laser on the human body. Conclusion: In conclusion, it was noted that the main phenomenon associated with laser therapy-induced improvement in the condition of knee OA patients is the downregulation of MMP2.
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INTRODUCTION AND OBJECTIVES: Amino acids are the most frequently reported metabolites associated with low bone mineral density (BMD) in metabolomics studies. We aimed to evaluate the association between amino acid metabolic profile and bone indices in the elderly population. METHODS: 400 individuals were randomly selected from 2384 elderly men and women over 60 years participating in the second stage of the Bushehr elderly health (BEH) program, a population-based prospective cohort study that is being conducted in Bushehr, a southern province of Iran. Frozen plasma samples were used to measure 29 amino acid and derivatives metabolites using the UPLC-MS/MS-based targeted metabolomics platform. We conducted Elastic net regression analysis to detect the metabolites associated with BMD of different sites and lumbar spine trabecular bone score, and also to examine the ability of the measured metabolites to differentiate osteoporosis. RESULTS: We adjusted the analysis for possible confounders (age, BMI, diabetes, smoking, physical activity, vitamin D level, and sex). Valine, leucine, isoleucine, and alanine in women and tryptophan in men were the most important amino acids inversely associated with osteoporosis (OR range from 0.77 to 0.89). Sarcosine, followed by tyrosine, asparagine, alpha aminobutyric acid, and ADMA in women and glutamine in men and when both women and men were considered together were the most discriminating amino acids detected in individuals with osteoporosis (OR range from 1.15 to 1.31). CONCLUSION: We found several amino acid metabolites associated with possible bone status in elderly individuals. Further studies are required to evaluate the utility of these metabolites as clinical biomarkers for osteoporosis prediction and their effect on bone health as dietary supplements.
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Densidade Óssea , Osteoporose , Idoso , Aminoácidos , Cromatografia Líquida , Feminino , Humanos , Masculino , Metabolômica , Osteoporose/diagnóstico , Osteoporose/epidemiologia , Estudos Prospectivos , Espectrometria de Massas em TandemRESUMO
BACKGROUND: Insulin resistance (IR) evolved from excessive energy intake and poor energy expenditure, affecting the patient's quality of life. Amino acid and acylcarnitine metabolomic profiles have identified consistent patterns associated with metabolic disease and insulin sensitivity. Here, we have measured a wide array of metabolites (30 acylcarnitines and 20 amino acids) with the MS/MS and investigated the association of metabolic profile with insulin resistance. METHODS: The study population (n = 403) was randomly chosen from non-diabetic participants of the Surveillance of Risk Factors of NCDs in Iran Study (STEPS 2016). STEPS 2016 is a population-based cross-sectional study conducted periodically on adults aged 18-75 years in 30 provinces of Iran. Participants were divided into two groups according to the optimal cut-off point determined by the Youden index of HOMA-IR for the diagnosis of metabolic syndrome. Associations were investigated using regression models adjusted for age, sex, and body mass index (BMI). RESULTS: People with high IR were significantly younger, and had higher education level, BMI, waist circumference, FPG, HbA1c, ALT, triglyceride, cholesterol, non-HDL cholesterol, uric acid, and a lower HDL-C level. We observed a strong positive association of serum BCAA (valine and leucine), AAA (tyrosine, tryptophan, and phenylalanine), alanine, and C0 (free carnitine) with IR (HOMA-IR); while C18:1 (oleoyl L-carnitine) was inversely correlated with IR. CONCLUSIONS: In the present study, we identified specific metabolites linked to HOMA-IR that improved IR prediction. In summary, our study adds more evidence that a particular metabolomic profile perturbation is associated with metabolic disease and reemphasizes the significance of understanding the biochemistry and physiology which lead to these associations.
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Resistência à Insulina , Síndrome Metabólica , Adolescente , Adulto , Idoso , Índice de Massa Corporal , Colesterol/sangue , Estudos Transversais , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Resistência à Insulina/fisiologia , Irã (Geográfico)/epidemiologia , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Fatores de Risco , Espectrometria de Massas em Tandem , Adulto JovemRESUMO
Preliminary studies also show that many of the fatalities of COVID-19 are due to over-activity of the immune system, and photobiomodulation (PBM) therapy mainly accelerates wound healing and reduces pain and inflammation. Therefore, this systematic review and meta-analysis was conducted to evaluate the probable effect of the PBM therapy on the lung inflammation or ARDS and accelerate the regeneration of the damaged tissue. We systematically searched major indexing databases, including PubMed/Medline, ISI web of science (WOS), Scopus, Embase, and Cochrane central, using standard terms without any language, study region, or type restrictions. Of the 438 studies found through initial searches, 13 met the inclusion criteria. After applying the exclusion criteria, the main properties of 13 articles on 384 animals included in this meta-analysis with a wide range of species include rat (n = 10) and rabbit (n = 3). The analysis revealed that PBM therapy reduced TNFα (SMD:-3.75, 95% CI: -4.49, -3.02, P < 0.00001, I2 = 10%), IL-1ß (SMD:-4.65, 95% CI: -6.15, -3.16, P < 0.00001, I2 = 62%), and IL-6 (SMD:-4.20, 95% CI: -6.42, -1.97, P = 0.0002, I2 = 88%) significantly compared with the model controls. Hence, PBM therapy increased IL-10 significantly compared with the model controls (SMD:-4.65, 95% CI: -6.15, -3.16, P < 0.00001, I2 = 62%). PBM therapy also reduced MPO activity (SMD:-2.13, 95% CI: -3.38, -0.87, P = 0.0009, I2 = 64%) and vascular permeability (SMD:-2.59, 95% CI: -4.40, -0.77, P = 0.0052, I2 = 71%) in the lung using the Evans blue extravasation technique significantly compared with the model controls. This systematic review and meta-analysis revealed that the PBM therapy does utilize beneficial anti-inflammatory effect, modulation of the immune system, lung permeability, or bronchoalveolar lavage on lung damage in both animal models and clinical studies. However, animal model and clinical studies appear limited considering the quality of the included evidences; therefore, large clinical trials are still required.
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COVID-19 , Terapia com Luz de Baixa Intensidade , Pneumonia , Animais , Inflamação , Pulmão , Coelhos , RatosRESUMO
Animal studies are recognized as a significant step forward in the bridging between drug discovery and clinical applications. Animal models, due to their relative genetic, molecular, physiological, and even anatomical similarities to humans, can provide a suitable platform for unraveling the mechanisms underlying human diseases and discovering new therapeutic approaches as well. Recently, zebrafish has attracted attention as a valuable experimental and pharmacological model in drug discovery and development studies due to its prominent characteristics such as the high degree of genetic similarity with humans, genetic manipulability, and prominent clinical features. Since advancing a theory to a valid and reliable observation requires the manipulation of animals, it is, therefore, essential to use efficient modeling methods appropriate to the different aspects of experimental conditions. In this context, applying several various approaches such as using chemicals, pathogens, and genetic manipulation approaches allows zebrafish development into a preferable model that mimics some human disease pathophysiology. Thus, such modeling approaches not only can provide a framework for a comprehensive understanding of the human disease mechanisms that have a counterpart in zebrafish but also can pave the way for discovering new drugs that are accompanied by higher amelioration effects on different human diseases.
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Descoberta de Drogas , Peixe-Zebra , Animais , Modelos Animais de Doenças , Descoberta de Drogas/métodos , Humanos , Peixe-Zebra/genéticaRESUMO
For a very long time, viral infections have been considered as one of the most important causes of death and disability around the world. Through the viral infection, viruses as small pathogens enter the host cells and use hosts' biosynthesis machinery to replicate and collect infectious lineages. Moreover, they can modify hosts' metabolic pathways in order to their own purposes. Nowadays (in 2019-2020), the most famous type of viral infection which was caused by a novel type of coronavirus is called COVID-19 disease. It has claimed the lives of many people around the world and is a very serious threat to health. Since investigations of the effects of viruses on host metabolism using metabolomics tools may have given focuses on novel appropriate treatments, in the current review the authors highlighted the virus-host metabolic interactions and metabolomics perspective in COVID-19.
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COVID-19 , Doenças Transmissíveis , Vírus , Humanos , Metabolômica , SARS-CoV-2RESUMO
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.
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Bioquímica , Biologia Computacional , Biologia Molecular , TecnologiaRESUMO
Mesenchymal stem cells (MSCs) are multipotent cells which are popular in human regenerative medicine. These cells can renew themselves and differentiate into several specialized cell types including osteoblasts, adipocytes, and chondrocytes under physiological and experimental conditions. MSCs can secret a lot of components including proteins and metabolites. These components have significant effects on their surrounding cells and also can be used to characterize them. This characterization of multipotent MSCs plays a critical role in their therapeutic potential. The metabolic profile of culture media verified by applying matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques. Also, the differentiation and development of MSCs have monitored through culture media metabolome or secretome (secreted metabolites). Totally, 24 potential metabolites were identified. Between them 12 metabolites are unique to BM-MSCs and 5 metabolites are unique to AD-MSCs. Trilineage differentiation including chondrocytes, osteoblasts, and adipocytes, as well as metabolites that are being differentiated, have been shown in different weeks. In the present study, the therapeutic effects of MSCs analyzed by decoding the metabolome for MSCs secretome via metabolic profiling using MALDI-TOF-MS techniques.
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Células-Tronco Mesenquimais , Humanos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Meios de Cultura/metabolismo , Diferenciação Celular , AdipócitosRESUMO
Background: In patients with diabetes, transplantation of stem cells increases C-peptide levels and induces insulin independence for some period. Today, this positive therapeutic outcome is widely attributed to the well-documented immunomodulatory properties of stem cells. The aim of this study was to report alternations (the trend of increase or decrease) in different lymphocyte populations in a stem cell clinical trial performed in our institute. Methods: Recorded data of a clinical trial conducted on 72 patients with type 1 diabetes who had received fetal stem cell transplantation several years ago and were regularly monitored before and after the procedure in 1, 3, 6, 12, 24 months were analyzed. In these regular follow-up visits, insulin demand, HbA1c, C-peptide, and alternation to B cell and T cell populations were analyzed and recorded. For the purpose of the current study, patients were retrospectively divided into 2 groups, namely, those with the positive response to treatment and patients without such response. Temporary positive therapeutic response was defined by 2 different indicators, namely, plasma C-peptide levels and insulin dose-adjusted A1C (IDAA1c), which was calculated as A1C (percent) + (4 × insulin dose (units per kilogram per 24 h). Data analysis was performed by means of SPSS Version 18. Results: Besides the short-term therapeutic effect, we observed remarkably significant alternations to the populations of B and T lymphocytes in the recipients. When patients were retrospectively assigned to 2 different groups of patients with a positive therapeutic response (based on C-peptide changes) and those without it, it was observed that alternations to different populations of B-cells and T-cells were significantly different in these 2 groups. Conclusion: Our results demonstrated that transplantation of stem cells leads to significant positive therapeutic outcomes in one group of patients who showed totally distinct patterns of alternation to different groups of lymphocytes.
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BACKGROUND: Recent studies have shown that obesity is associated with the severity of coronavirus disease (COVID-19). We reviewed clinical studies to clarify the obesity relationship with COVID-19 severity, comorbidities, and discussing possible mechanisms. MATERIALS AND METHODS: The electronic databases, including Web of Science, PubMed, Scopus, and Google Scholar, were searched and all studies conducted on COVID-19 and obesity were reviewed. All studies were independently screened by reviewers based on their titles and abstracts. RESULTS: Forty relevant articles were selected, and their full texts were reviewed. Obesity affects the respiratory and immune systems through various mechanisms. Cytokine and adipokine secretion from adipose tissue leads to a pro-inflammatory state in obese patients, predisposing them to thrombosis, incoordination of innate and adaptive immune responses, inadequate antibody response, and cytokine storm. Obese patients had a longer virus shedding. Obesity is associated with other comorbidities such as hypertension, cardiovascular diseases, diabetes mellitus, and vitamin D deficiency. Hospitalization, intensive care unit admission, mechanical ventilation, and even mortality in obese patients were higher than normal-weight patients. Obesity could alter the direction of severe COVID-19 symptoms to younger individuals. Reduced physical activity, unhealthy eating habits and, more stress and fear experienced during the COVID-19 pandemic may result in more weight gain and obesity. CONCLUSIONS: Obesity should be considered as an independent risk factor for the severity of COVID-19. Paying more attention to preventing weight gain in obese patients with COVID-19 infection in early levels of disease is crucial during this pandemic.