RESUMO
BACKGROUND: Obesity, a global challenge, is a complex disorder linked to various diseases. Different kinds of treatments are currently used to treat or control this pandemic. Despite their positive effects on controlling obesity, they still have limitations and side effects including digestive problems, difficulties of daily infusion of some drugs, surgical complications, and weight regain. All these issues cause these conventional methods not to have desirable efficacy. In this regard, brown adipose tissue (BAT) transplantation as a new investigational treatment is proposed, which has beneficial effects with no documented side effect in studies up to now. METHODS: This systematic review protocol was registered in the International Prospective Register of Systematic Reviews (Registration Number: CRD42018110045). The systematical search was conducted on Web of Science, Scopus, PubMed, Embase, and ProQuest databases. The quality assessments in the included studies and data gathering were conducted independently by two authors. The main variables were anthropometric indices including body weight, levels of leptin, IGF-1, glucagon, adiponectin, fasting blood glucose, and UCP-1. RESULTS: Following the search in mentioned databases, ten articles were entered into this systematic review. In most studies, weight gain and white adipocyte size were reduced in the BAT transplant group. It seems that the transplantation leads to the regeneration of healthy adipose tissue by activating the endogenous BAT. CONCLUSIONS: Since BAT transplantation is one of the possible future treatments of obesity, many studies are conducted to evaluate the outcomes and related procedures precisely, so it can finally step into clinical application.
Assuntos
Tecido Adiposo Marrom/transplante , Obesidade/terapia , Adiponectina/sangue , Animais , Glicemia/análise , Modelos Animais de Doenças , Feminino , Leptina/sangue , Masculino , Camundongos , Camundongos ObesosRESUMO
Although stem cells have the most therapeutic potential, the advantages of regenerative medicine may be best provided using extracellular vesicles which also known in the past as "cellular dust." These microparticles are substances released by cells and play a pivotal role in pathophysiology of tumor progression and metastasis, thrombosis, and inflammation. Extracellular vesicles including exosomes and cell-derived microparticles supporting many physiological and disease processes which are relevant to immunology, hemostasis, thrombosis, neurobiology, cell signaling, angiogenesis, and cancer. While they have not any value for many years, this cellular dust has been studied and shows therapeutic properties similar to their mother cells (stem cells) but without their disadvantages. These vesicles do not divide, limiting the risk of cancer, and do not differentiate either. Therefore, they prevent tumor progression and development of poor function. Furthermore, it appears that they can be produced by a single donor for several patients, and have already confirmed their therapeutic potential in animals in repairing heart, liver and kidney lesions. The present study was aimed to introduce cellular dust as a new horizon for regenerative cancer medicine and also new hope for potential therapeutic applications of cancer and associated diseases.
Assuntos
Vesículas Extracelulares , Oncologia/métodos , Neoplasias/terapia , Medicina Regenerativa/métodos , Animais , Micropartículas Derivadas de Células , Exossomos , HumanosRESUMO
Gene therapy as a novel study in molecular medicine will have a significant impact on human health in the near future. In recent years, the scope of gene therapy has been developed and is now beginning to revolutionize therapeutic approaches. Accordingly, many types of diseases are now being studied and treated in clinical trials through various gene delivery vectors. The emergence of recombinant DNA technology which provides the possibility of fetal genetic screening and genetic counseling is a good case in point. Therefore, gene therapy advances are being applied to correct inherited genetic disorders such as hemophilia, cystic fibrosis, and familial hypercholesterolemia as well as acquired diseases like cancer, AIDS, Alzheimer's disease, Parkinson's disease, and infectious diseases like HIV. As a result, gene therapy approaches have the ability to help the vast majority of newborns with different diseases. Since these ongoing treatments and clinical trials are being developed, many more barriers and challenges have been created. In order to continue this positive growth, these challenges need to be recognized and addressed. Accordingly, safety, efficiency and also risks and benefits of gene therapy trials for each disease should be considered. As a result, sustained manufacturing of the therapeutic gene product without any harmful side effects is the least requirement for gene therapy. Herein, different aspects of gene therapy, an overview of the progress, and also the prospects for the future have been discussed for the successful practice of gene therapy.
Assuntos
Doença , Terapia Genética/métodos , Técnicas de Transferência de Genes , Vetores Genéticos , HumanosRESUMO
BACKGROUND: Chikungunya virus (CHIKV) is a widespread mosquito-borne virus representing a serious challenge to public health. The largest outbreak in the Middle-East was recorded in 2016-2017 in Pakistan. Sistan and Baluchistan Province of Iran shares a wide border with Pakistan; accordingly, introduction of CHIKV from Pakistan to Iran seems to be probable. The current study is aimed at investigating CHIKV infection in Sistan and Baluchistan Province. METHODS: Between April 2017 and June 2018, a total of 159 serum samples of CHIK suspected cases from 10 cities of Sistan and Baluchistan Province were tested by molecular and serological assays. Samples obtained up to 4 days after onset of illness were tested by real time PCR (n = 8). Samples collected 5-10 days after disease onset were subjected to ELISA, as well as real time PCR tests (n = 72). Samples obtained after the 10th day of disease onset were tested by only ELISA (n = 79). Phylogenetic analysis of real time PCR positive samples was carried out by sequencing of a 1014-bp region of Envelope 1 gene (E1 gene). Chi-square and independent t tests were used to evaluate the association between variables and CHIKV infection. RESULTS: In total, 40 (25.1%) out of 159 samples tested positive either by real time PCR or ELISA tests.Out of 151 samples serologically analyzed, 19 (12.6%) and 28 (18.6%) cases were positive for anti-CHIKV IgM and anti-CHIKV IgG antibodies, respectively. Of 80 samples tested by real time PCR, CHIKV RNA was detected in 11 (13.7%) sera, all of them had recent travel history to Pakistan. Additionally, phylogenetic analysis of 5 samples indicated their similarity with recent isolates of Pakistan outbreak 2016-2017 belonging to Indian Ocean sub-lineage of ECSA genotype. A significant correlation between abroad travel history and CHIKV infection was observed (P < 0.001). The most common clinical symptoms included fever, arthralgia/arthritis, myalgia, headache, and chill. CONCLUSIONS: These results present substantial evidence of CHIKV introduction to Iran from Pakistan and emphasize the need for the enhancement of surveillance system and preventive measures.
Assuntos
Febre de Chikungunya/epidemiologia , Vírus Chikungunya/genética , Vírus Chikungunya/imunologia , Doenças Transmissíveis Importadas/virologia , Surtos de Doenças , Adolescente , Adulto , Animais , Anticorpos Antivirais/sangue , Artralgia/epidemiologia , Vírus Chikungunya/isolamento & purificação , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Febre/epidemiologia , Genótipo , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Mosquitos Vetores/virologia , Paquistão/epidemiologia , Filogenia , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Viagem , Proteínas do Envelope Viral/genética , Adulto JovemAssuntos
Vírus da Febre Hemorrágica da Crimeia-Congo/genética , Febre Hemorrágica da Crimeia/virologia , Adulto , Genótipo , Vírus da Febre Hemorrágica da Crimeia-Congo/classificação , Vírus da Febre Hemorrágica da Crimeia-Congo/isolamento & purificação , Humanos , Irã (Geográfico) , Masculino , FilogeniaRESUMO
Key Clinical Message: The identification of a novel RP1 gene mutation highlights the importance of precise variant identification for retinitis pigmentosa prognosis and genetic consultations, emphasizing comprehensive genetic analysis for personalized care. Abstract: Our study unveils a noteworthy association between retinitis pigmentosa-1 and a newly discovered homozygous mutation (c.5326delC; p.Asp1777Ilefs*32) within the RP1 gene. This highlights the crucial role of accurate variant identification in not only informing prognosis but also improving genetic consultations and influencing future diagnostic approaches for individuals affected by retinitis pigmentosa.
RESUMO
Different biomaterials have been used as biological dressing for wound regeneration. For many decades, human amniotic membrane graft (AM) has been widely applied for treating acute and chronic wounds. It has minimal toxicity and immunogenicity, supports mesenchymal cell in-growth, improves epidermal cell adherence and proliferation, and finally is inexpensive and readily available. Enrichment of tissue grafts with the stem cells is a new approach to improve their regenerative effects. This animal study aimed at investigating feasibility, safety, and efficacy of tissue-engineered dressings composed of AM and two different types of mesenchymal stem cells (MSCs) in the excisional wound model in rats. Human adipose-derived MSCs (ADMSCs) and placenta-derived MSCs (PLMSCs) were manufactured from the donated adipose and placenta tissues respectively. After cell characterization, MSCs were seeded on acellular AM (AAM) and cultivated for 5 days. Excisional wound model was developed in 24 male Wistar rats that were randomly classified into four groups including control, AAM, ADMSCs + AAM, and PLMSCs + AAM (n = 6 in each group). Tissue-engineered constructs were applied, and photographs were taken on days 0, 7, and 14 for observing the wound healing rates. In days 7 and 14 post-treatment, three rats from each group were euthanized, and wound biopsies were harvested, and histopathologic studies were conducted. The results of wound closure rate, re-epithelialization, angiogenesis, and collagen remodeling demonstrated that in comparison with the control groups, the MSC-seeded AAMs had superior regenerative effects in excisional wound animal model. Between MSCs group, the PLMSCs showed better healing effect. Our data suggested that seeding of MSCs on AAM can boosts its regenerative effects in wound treatment. We also found that PLMSCs had superior regenerative effects to ADMSc in the rat model of excisional wound.
Assuntos
Âmnio , Células-Tronco Mesenquimais , Animais , Bandagens , Masculino , Ratos , Ratos Wistar , CicatrizaçãoRESUMO
Recently, gene therapy as one of the most promising treatments can apply genes for incurable diseases treatment. In this context, vectors as gene delivery systems play a pivotal role in gene therapy procedure. Hereupon, viral vectors have been increasingly introduced as a hyper-efficient tools for gene therapy. Adenoviral vectors as one of the most common groups which are used in gene therapy have a high ability for humans. Indeed, they are not integrated into host genome. In other words, they can be adapted for direct transduction of recombinant proteins into targeted cells. Moreover, they have large packaging capacity and high levels of efficiency and expression. In accordance with translational pathways from the basic to the clinic, recombinant adenoviral vectors packaging must be managed under good manufacturing practice (GMP) principles before applying in clinical trials. Therein, in this chapter standard methods for manufacturing of GMP-compliant Adenoviral vectors for gene therapy have been introduced.
Assuntos
Adenoviridae/genética , Tecnologia Biomédica/normas , Terapia Genética/métodos , Vetores Genéticos/normas , Adenoviridae/fisiologia , Tecnologia Biomédica/métodos , Técnicas de Transferência de Genes/normas , Terapia Genética/normas , Células HEK293 , Humanos , Guias de Prática Clínica como Assunto , Empacotamento do Genoma Viral , Replicação ViralRESUMO
Breast cancer is a heterogeneous disease, which is the consequence of several genetic and environmental factors. Also, it is one of the most common causes of cancer death and second leading cancer among women all around the world. Therefore, it is necessary to develop novel therapeutic approaches useful for the successful treatment of breast cancer. As conventional treatments had limited success, alternative approaches for the treatment of breast cancer have been applied in recent years. Hence, the molecular basis of breast cancer has provided the opportunity of using genetic materials for therapeutic uses. In this regard, gene therapy as one of the potentially efficient and beneficial treatments among various techniques became a popular treatment for different cancers, especially breast cancer. Accordingly, there are plenty of targets available for gene therapy of breast cancer. Gene therapy strategies have the potential to correct molecular defects that contributed to the cancer progression. These techniques should selectively target tumor cells without affecting normal cells. Moreover, data of clinical trials in gene therapy for breast cancer indicated that this approach has little toxicity compared to other therapeutic approaches. In this study, different aspects of breast neoplasm, gene therapy techniques, challenges, and recent developments will be mentioned.
Assuntos
Neoplasias da Mama , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Feminino , Terapia Genética , HumanosRESUMO
Background Although macular amyloidosis is a relatively rare disease, it is a common cutaneous disease in Asia and the Middle East. On hematoxylin and eosin (H&E) stained slides, early lesions could easily be missed without the use of special stains and/or immunohistochemistry. Methods We enrolled 42 patients with the clinical impression of macular amyloidosis who had undergone two 4-mm punch biopsies from 2015 to 2016 at a dermatology clinic affiliated to Shiraz University. Besides, 14 cases with a clinical diagnosis other than macular amyloidosis were selected as the negative control group. Congo red, crystal violet, and immunohistochemical (IHC) staining of CK5 and high molecular weight keratin (HMWK) were performed for each specimen. Results H&E slides showed globular depositions in 15 (35.7%) out of 42 patients. None of the patients showed apple-green birefringence with Congo red stain. Evaluation of crystal violet stained sections revealed purplish violet amyloid deposits in 15 (35.7%) patients. IHC study showed expression of CK5 in 52.4% and HMWK in 50% of the patients, which was not a significant difference (p = 0.715). The findings of both IHC markers had a significant difference with H&E stains (p = 0.039) and crystal violet (p = 0.008). Additionally, we found that two punch biopsies from two sites in the involved area did not have a significant preference over one punch biopsy. All of the cases in the control group were negative for amyloid deposition in H&E, special stains, and IHC stained slides as expected. Conclusions IHC evaluation using CK5 and HMWK might be a useful tool for diagnosing macular amyloidosis.
RESUMO
PURPOSE: The healing process is impaired in diabetic wounds like the other types of chronic wounds. Cytokines, and growth factors are valuable candidates for determination of wound vitality or duration. The aim of this study is to introduce a beneficial method to stop the inflammatory phase and infection in the wound healing process for accelerating the treatment of diabetic foot ulcers. METHODS: As a randomized controlled trial, 44 patients with diabetic foot ulcers were selected and randomized. Twenty-two patients received standard care and rest of them received SC (standard care) + CAP (cold atmospheric plasma), n = 22). Clinical examination was performed to assess the status of peripheral nerves and arteries for all patients. Cold plasma jet was used as a source of helium gas plasma generator. Plasma was irradiated on the wound 5 min, 3 times a week for 3 consecutive weeks. RESULTS: Applying a plasma jet was effective in wound healing. The level of inflammatory cytokines was changed. Moreover, after applying plasma the mean expression of these variables was significantly decreased (P = 0.001). Following the plasma treatment, the level of cytokines such as IL-1 (39.44 ± 7.67), IL-8 (368.30 ± 82.43), INF-γ (17.03 ± 2.62), TNFα (22.75 ± 4.02) has decreased, inflammatory factors have ameliorated over three weeks, and accelerate wound healing. After CAP exposure, the mean of the mean fraction of bacterial load counts was significantly decreased. CONCLUSION: The effect of plasma irradiation on infectious diabetic foot ulcer was decreased bacterial load then accelerated wound healing by effecting on inflammatory phase in diabetic foot ulcers.
RESUMO
OBJECTIVES: The pace of population aging is growing rapidly around the world. Aging is associated with the emergence of different health status including geriatric syndrome such as frailty, diabetes, cardiovascular diseases, and dementia. These conditions are the most prominent challenges for health care systems and also elderly people. Therefore, understanding these changes can help scientists to prevent and treat significant health issues and also improve the functional ability of older adults. METHODS: This is a protocol of the first wave of Birjand Longitudinal Aging Study that is an ongoing community-based prospective cohort study with a following up at least 10 years. This study carries out on aged population ≥ 60 years which were residents in Birjand County (urban and rural older subjects). The selection of the participants of this study in urban areas is based on an age group weighted multistage stratified random sample while in the rural region the sample was selected from all ten rural regions of Birjand County by simple random sampling. The rural region sampling was based on the list of the aged population which were under the coverage of the rural health center. Sociodemographic, past medical history, lifestyle, sleep, activities of daily living, cognitive function, quality of life, and social capital were evaluated by interviewing with the participants and one of the informants. Anthropometric measures, electrocardiography, and interpretation of ophthalmologic examination were carried out by experts. Fasting Blood samples were collected and bio-banked in - 80 °C. then finally biochemical and hematologic markers were measured. RESULTS: This is the protocol of stage one baseline of Birjand Longitudinal Aging Study (BLAS). The BLAS is an enjoining study, the first phase of its baseline was carried out on a community- dwelling aged population sample ≥ 60 years who were residents in urban and rural regions of Birjand County. This is a community based prospective cohort study with at least 10 years follow up of participants. The data for 65% of older subjects (response rate = 65%) that lived in clusters were collected. CONCLUSIONS: This study can help scientists to recognize some risk factors related to the aging process and also aware policymakers about the necessity to create heath care services at regional and even national levels.
RESUMO
Food contamination by heavy metals can lead to the accumulation of these elements in the body of consumers and the contraction of diseases. Accordingly, heavy metal concentration in common carp fishes consumed in Shiraz, Iran was determined in the present study. The mean concentrations of Pb, Cd, Zn, and Cu were 0.23, 0.07, 0.47, and 0.59â¯mg/kg (dry weight), respectively. The average concentration of heavy metals in the muscle of common carps consumed in Shiraz was less than the permissible standard of the WHO and FAO. The estimated weekly intake (EWI) of the studied metals was below the provisional tolerable weekly intake (PTWI). The maximum and minimum relative risk (RR) equaled 48.93 and 0.55% of the total risk for Cd and Zn, respectively.