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BACKGROUND: Ischemia-reperfusion Injury (IRI) is a complex pathophysiological process with severe consequences, including irreversible loss of renal function. Various intraoperative prevention methods have been proposed to mitigate the harmful effects of warm ischemia and kidney reperfusion. AIM: This comprehensive analysis provides an overview of pharmacological agents and intraoperative methods for preventing and treating renal IRI. METHODS: Our analysis revealed that eplerenone exhibited the highest binding affinity to crucial targets, including Aldehyde Dehydrogenase (AD), Estrogen Receptor (ER), Klotho protein, Mineralocorticoid Receptor (MR), and Toll-like Receptor 4 (TLR4). This finding indicates eplerenone's potential as a potent preventive agent against IRI, surpassing other available therapeutics like Benzodioxole, Hydrocortisone, Indoles, Nicotinamide adenine dinucleotide, and Niacinamide. In preventing kidney IRI, our comprehensive analysis emphasizes the significance of eplerenone due to its strong binding affinity to key targets involved in the pathogenesis of IRI. RESULTS: This finding positions eplerenone as a promising candidate for further clinical investigation and consideration for future clinical practice. CONCLUSION: The insights provided in this analysis will assist clinicians and researchers in selecting effective preventive approaches for renal IRI in surgical settings, potentially improving patient outcomes.
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Traumatismo por Reperfusão , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Humanos , Animais , Simulação por Computador , Rim/efeitos dos fármacos , Rim/metabolismoRESUMO
In this study, we propose a spatially patterned 3D-printed nanohydroxyapatite (nHA)/beta-tricalcium phosphate (ß-TCP)/collagen composite scaffold incorporating human dental pulp-derived mesenchymal stem cells (hDP-MSCs) for bone regeneration in critical-sized defects. We investigated angiogenesis and osteogenesis in a rabbit critical-sized mandibular defect model treated with this engineered construct. The critical and synergistic role of collagen coating and incorporation of stem cells in the regeneration process was confirmed by including a cell-free uncoated 3D-printed nHA/ß-TCP scaffold, a stem cell-loaded 3D-printed nHA/ß-TCP scaffold, and a cell-free collagen-coated 3D-printed nHA/ß-TCP scaffold in the experimental design, in addition to an empty defect. Posteuthanasia evaluations through X-ray analysis, histological assessments, immunohistochemistry staining, histomorphometry, and reverse transcription-polymerase chain reaction (RT-PCR) suggest the formation of substantial woven and lamellar bone in the cell-loaded collagen-coated 3D-printed nHA/ß-TCP scaffolds. Histomorphometric analysis demonstrated a significant increase in osteoblasts, osteocytes, osteoclasts, bone area, and vascularization compared to that observed in the control group. Conversely, a significant decrease in fibroblasts/fibrocytes and connective tissue was observed in this group compared to that in the control group. RT-PCR indicated a significant upregulation in the expression of osteogenesis-related genes, including BMP2, ALPL, SOX9, Runx2, and SPP1. The findings suggest that the hDP-MSC-loaded 3D-printed nHA/ß-TCP/collagen composite scaffold is promising for bone regeneration in critical-sized defects.
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Regeneração Óssea , Fosfatos de Cálcio , Cerâmica , Hidrogéis , Mandíbula , Neovascularização Fisiológica , Impressão Tridimensional , Alicerces Teciduais , Animais , Coelhos , Regeneração Óssea/efeitos dos fármacos , Alicerces Teciduais/química , Humanos , Cerâmica/química , Fosfatos de Cálcio/química , Hidrogéis/química , Osteogênese/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Colágeno/química , Durapatita/química , Engenharia Tecidual/métodos , Polpa Dentária/citologia , Modelos Animais de Doenças , Masculino , AngiogêneseRESUMO
Background: Cervical cancer poses a considerable worldwide health issue, where infection with the human papillomavirus (HPV) plays a vital role as a risk factor. Photodynamic therapy (PDT) is a minimally invasive treatment for HPV-related cervical lesions, which uses photosensitizers and light to selectively destroy abnormal cells. Objectives: Our objective is to present a comprehensive overview of the different types of molecules employed in PDT to reduce the occurrence and fatality rates associated with cervical cancer. Design: Scoping review and bibliometric analysis. Methods: The article explores clinical trials investigating the efficacy of PDT in treating low-grade squamous intraepithelial lesion and high-grade squamous intraepithelial lesion, as well as preclinical approaches utilizing various molecules for PDT in cervical cancer. Furthermore, the article sheds light on potential molecules for PDT enhancement, examining their properties through computer modeling simulations, molecular docking, and assessing their advantages and disadvantages. Results: Our findings demonstrate that PDT holds promise as a therapeutic approach for treating cervical lesions associated with HPV and cervical cancer. Additionally, we observe that the utilization of diverse dye classes enhances the anticancer effects of PDT. Conclusion: Among the various molecules employed in PDT, functionalized fullerene exhibits a notable inclination toward overexpressed receptors in cervical cancer cells, making it a potential candidate for intensified use in PDT. However, further research is needed to evaluate its long-term effectiveness and safety.
Using light to treat cervical cancer: what you need to know Cervical cancer is a significant global health concern, often linked to the human papillomavirus (HPV). There is a less invasive treatment called photodynamic therapy (PDT), which employs light and special substances to target and destroy abnormal cells related to HPV. In this review, we aim to give you a comprehensive look at the different substances used in PDT to reduce the occurrence and severity of cervical cancer. We have examined clinical trials focusing on treating specific types of cervical lesions and explored preclinical approaches using various substances. We have also delved into computer simulations and molecular docking to understand the strengths and weaknesses of these substances. Our findings show that PDT has potential as a treatment for HPV-related cervical lesions and cancer. Different dye classes used in this therapy enhance its effectiveness against cancer. Notably, a substance called functionalized fullerene stands out for its tendency to target receptors overexpressed in cervical cancer cells. It looks promising, but more research is necessary to ensure its long-term effectiveness and safety.
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Introduction: The prevalence of non-communicable diseases (NCDs) is increasing worldwide. Several modifiable risk factors, such as smoking, alcohol drinking, physical inactivity, and obesity, have been linked to the development of NCDs in both genders. Understanding the prevalence of these risk factors and their associated factors is crucial for effective intervention planning in adult populations. This study aimed to provide an overview of the prevalence and associated factors of these risk behaviors among different genders of adults in West Kazakhstan. Methods: A cross-sectional study was conducted in four regions of West Kazakhstan. A stratified multistage sampling technique was utilized to obtain a representative sample size of 4,800 participants aged 18 -69 years. Trained researchers administered face-to-face interviews using validated questionnaires to gather information pertaining to sociodemographic characteristics, smoking habits, alcohol drinking, dietary patterns, physical activity levels, body mass index (BMI), and prevalent diseases. Results: This study, which included 4,800 participants from West Kazakhstan, revealed some striking numerical findings. The overall prevalence rates of behavioral risk factors and metabolic conditions were as follows: smoking was 13.6% (95%CI: 3.2-24.0%), alcohol drinking was 47.0% (27.7-66.3%), current obesity was 22.3% (9.0-35.6%), and physical inactivity was 80.7% (55.4-106.0%). In addition, the overall prevalence rates of metabolic conditions were 25.6% (11.3-39.9%) for hypertension, 7.5% (0.2-15.2%) for diabetes, 11.8% (2.1-21.5%) for high cholesterol, and 13.0% (2.8-23.2%) for cardiovascular diseases. Additionally, a higher prevalence of high cholesterol was observed in men, and a greater prevalence of heart disease was identified in women. Multinomial logistic regression revealed that physical inactivity was associated with hypertension, diabetes, and heart disease, while obesity was linked to hypertension, high cholesterol, and heart disease. Discussion: This study in West Kazakhstan identified variations in the prevalence of behavioral risk factors and NCDs, highlighting gender, age, and regional disparities. Notably, men showed higher rates of smoking and alcohol drinking, while women exhibited a greater prevalence of physical inactivity and obesity. Gender and regional differences were evident, with the West Kazakhstan region standing out for distinct patterns. Tailored interventions are crucial to address these disparities and enhance public health in the region.
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Diabetes Mellitus , Cardiopatias , Hipertensão , Doenças não Transmissíveis , Adulto , Feminino , Humanos , Masculino , Prevalência , Estudos Transversais , Doenças não Transmissíveis/epidemiologia , Cazaquistão/epidemiologia , Fatores de Risco , Obesidade/epidemiologia , Obesidade/complicações , Hipertensão/epidemiologia , Diabetes Mellitus/epidemiologia , ColesterolRESUMO
The asymptomatic progression of chemotherapy-induced cardiotoxicity poses a significant risk to breast cancer patients. In the present single-center cohort study, a predictive model for evaluating the risk of cardiotoxicity during or by the end of chemotherapy was designed. The risk-prediction nomogram was delineated and assessed. In total, 34 patients out of 120 developed asymptomatic cardiotoxicity (28.3%). Of six explored biomarkers, only B-type natriuretic peptide showed a reliable pattern of incremental increase, revealing statistical significance between cardiotoxicity "+" and "-" groups by visit 4 or by the 9th month of monitoring (p 0.006). The following predictors were included in the model: age, hypertension, diabetes mellitus, baseline glomerular filtration rate, 6 min walk test measured at visit 4, BNP values at visit 4, left ventricular ejection fraction levels at visit 4, a total dose of radiotherapy received, and anthracycline cumulative doses. The model's AUC was 0.72 (95% CI 0.59; 0.86), evidencing the satisfactory predictive ability of the model; sensitivity 100% (95% CI 90.36; 100.0) at a specificity of 66.67% (95% CI 50.33; 79.79); PPV 54.1% [95% CI 47.13; 60.91]; PVN 100% [95% CI 94.64; 100.00]. The calibration plot showed satisfactory agreement between predicted and actual chances (p = 0.98). The designed model can be applied in settings lacking speckle tracking echocardiography.
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Introduction: Premature ovarian insufficiency (POI) is a challenging issue in terms of reproduction biology. In this study, therapeutic properties of bone marrow CD146+ mesenchymal stem cells (MSCs) and CD144+ endothelial cells (ECs) were separately investigated in rats with POI. Methods: POI rats were classified into control POI, POI + CD146+ MSCs, and POI + CD144+ ECs groups. Enriched CD146+ MSCs and CD144+ ECs were directly injected into ovarian tissue (15 × 104 cells/10 µL) in relevant groups. After 4 weeks, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels were measured in blood samples. Ovarian tissues were collected and subjected to Hematoxylin-Eosin and Masson's trichrome staining. The expression of angp-2, vegfr-2, smad-2, -4, -6, and tgf-ß1 was studied using qRT-PCR analysis. Histopathological examination indicated an increased pattern of atretic follicles in the POI group related to the control rats (P<0.0001). Results: Data indicated that injection of POI + CD146+ MSCs and CD144+ ECs in POI rats reduced atretic follicles and increased the number of normal follicles (P<0.01). Along with these changes, the content of blue-colored collagen fibers was diminished after cell transplantation. Besides, cell transplantation in POI rats had the potential to reduce increased FSH, and LH levels (P<0.05). In contrast, E2 content was increased in POI + CD146+ MSCs and POI + CD144+ ECs groups compared to control POI rats, indicating restoration of follicular function. CD144+ (smad-2, and -4) and CD146+ (smad-6) cells altered the activity of genes belonging TGF-ß signaling pathway. Unlike POI + CD146+ MSCs, aberrant angiogenesis properties were significantly down-regulated in POI + CD144+ ECs related to the control POI group (P<0.05). Conclusion: The transplantation of bone marrow CD146+ and CD144+ cells can lead to the restoration of ovarian tissue function in POI rats via modulating different mechanisms associated with angiogenesis and fibrosis.
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Three-dimensional nanofiber scaffolds offer a promising method for simulating in vivo conditions within the laboratory. This study aims to investigate the influence of a bilayer amniochorionic membrane/nanofibrous fibroin scaffold on the differentiation of human menstrual blood mesenchymal stromal/stem cells (MenSCs) into female germ cells. MenSCs were isolated and assigned to four culture groups: (i) MenSCs co-cultured with granulosa cells (GCs) using the scaffold (3D-T group), (ii) MenSCs using the scaffold alone (3D-C group), (iii) MenSCs co-cultured only with GCs (2D-T group), and (iv) MenSCs without co-culture or scaffold (2D-C group). Both MenSCs and GCs were independently cultured for two weeks before co-culturing was initiated. Flow cytometry was employed to characterize MenSCs based on positive markers (CD73, CD90, and CD105) and negative markers (CD45 and CD133). Additionally, flow cytometry and immunocytochemistry were used to characterize the GCs. Differentiated MenSCs were analyzed using real-time PCR and immunostaining. The real-time PCR results demonstrated significantly higher levels of VASA expression in the 3D-T group compared to the 3D-C, 2D-T, and 2D-C groups. Similarly, the SCP3 mRNA level in the 3D-T group was notably elevated compared to the 3D-C, 2D-T, and 2D-C groups. Moreover, the expression of GDF9 was significantly higher in the 3D-T group when compared to the 3D-C, 2D-T, and 2D-C groups. Immunostaining results revealed a lack of signal for VASA, SCP3, or GDF9 markers in the 2D-T group, while some cells in the 3D-T group exhibited positive staining for all these proteins. These findings suggest that the combination of a bilayer amniochorionic membrane/nanofibrous fibroin scaffold with co-culturing GCs facilitates the differentiation of MenSCs into female germ cells.
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Fibroínas , Células-Tronco Mesenquimais , Feminino , Humanos , Fibroínas/química , Alicerces Teciduais/química , Âmnio , Diferenciação Celular , Células Germinativas , Células CultivadasRESUMO
In the current study, we investigated the regenerative effects of amniotic fluid exosomes (AF-Exos) in a rat model for premature ovarian insufficiency (POI). POI is a condition characterized by a decrease in ovarian function that can lead to infertility. We induced POI by administering cyclophosphamide (CTX) for 15 consecutive days, and then transplanted AF-Exos directly into both ovarian tissues. Four weeks later, we measured the serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2), and performed histopathological evaluations using H & E and Masson's trichrome staining. We also monitored the expression of genes related to the TGF-ß signaling pathway using real-time PCR and examined the fertility rate of POI rats after AF-Exos therapy. Histological analysis showed an increase in atretic follicles and a decrease in healthy follicle count after POI induction. Four weeks post-AF-Exos intervention, the healthy follicle count increased (p < 0.01) while the atretic follicle count decreased (p < 0.001). In parallel, the deposition of collagen fibers also decreased following AF-Exos transplantation. The concentrations of FSH and LH hormones in sera remained unchanged after injection of AF-Exos, while E2 levels increased (p < 0.05). The expression of Smad-4 (p < 0.01) and Smad-6 (p < 0.05) was upregulated in POI rats that received AF-Exos, while Smad-2, TGF-ß1, TNF-α, and IL-10 remained statistically unchanged. Our records showed a notable increase in litter number after AF-Exos compared to the non-treated POI rats. These results suggest that AF-Exos transplantation has the potential to restore ovarian function through the TGF-ß/Smads signaling pathway in POI rats.
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Exossomos , Menopausa Precoce , Insuficiência Ovariana Primária , Animais , Feminino , Ratos , Líquido Amniótico/metabolismo , Exossomos/metabolismo , Hormônio Foliculoestimulante , Insuficiência Ovariana Primária/terapia , Transdução de Sinais , Fator de Crescimento Transformador betaRESUMO
Lung cancer is one of the most lethal malignancies in the world. However, current curative approaches for treating this type of cancer have some weaknesses. Therefore, scientists are attempting to discover new anti-lung cancer agents. Sea cucumber is a marine-derived source for discovering biologically active compounds with anti-lung cancer properties. To explore the anti-lung cancer properties of sea cucumber, we analyzed surveys using VOSviewer software and identified the most frequently used keywords. We then searched the Google Scholar database for compounds with anti-lung cancer properties within that keyword family. Finally, we used AutoDock 4 to identify the compounds with the highest affinity for apoptotic receptors in lung cancer cells. The results showed that triterpene glucosides were the most frequently identified compounds in studies examining the anti-cancer properties of sea cucumbers. Intercedenside C, Scabraside A, and Scabraside B were the three triterpene glycosides with the highest affinity for apoptotic receptors in lung cancer cells. To the best of our knowledge, this is the first time that anti-lung cancer properties of sea cucumber-derived compounds have been examined in in silico conditions. Ultimately, these three components displayed anti-lung cancer properties in in silico conditions and may be used for the manufacture of anti-lung cancer agents in the near future.
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Antineoplásicos , Neoplasias Pulmonares , Pepinos-do-Mar , Triterpenos , Animais , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Antineoplásicos/farmacologia , Glicosídeos , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Bibliometria , Estrutura MolecularRESUMO
Nowadays, major attention is being paid to curing different types of cancers and is focused on natural resources, including oceans and marine environments. Jellyfish are marine animals with the ability to utilize their venom in order to both feed and defend. Prior studies have displayed the anticancer capabilities of various jellyfish. Hence, we examined the anticancer features of the venom of Cassiopea andromeda and Catostylus mosaicus in an in vitro situation against the human pulmonary adenocarcinoma (A549) cancer cell line. The MTT assay demonstrated that both mentioned venoms have anti-tumoral ability in a dose-dependent manner. Western blot analysis proved that both venoms can increase some pro-apoptotic factors and reduce some anti-apoptotic molecules that lead to the inducing of apoptosis in A549 cells. GC/MS analysis demonstrated some compounds with biological effects, including anti-inflammatory, antioxidant and anti-cancer activities. Molecular docking and molecular dynamic showed the best position of each biologically active component on the different death receptors, which are involved in the process of apoptosis in A549 cells. Ultimately, this study has proven that both venoms of C. andromeda and C. mosaicus have the capability to suppress A549 cells in an in vitro condition and they might be utilized in order to design and develop brand new anticancer agents in the near future.
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Adenocarcinoma , Cnidários , Venenos de Cnidários , Neoplasias Pulmonares , Cifozoários , Animais , Humanos , Venenos de Cnidários/farmacologia , Venenos de Cnidários/química , Células A549 , Simulação de Acoplamento Molecular , Adenocarcinoma/tratamento farmacológico , Apoptose , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
Marine invertebrates are multicellular organisms consisting of a wide range of marine environmental species. Unlike vertebrates, including humans, one of the challenges in identifying and tracking invertebrate stem cells is the lack of a specific marker. Labeling stem cells with magnetic particles provides a non-invasive, in vivo tracking method using MRI. This study suggests antibody-conjugated iron nanoparticles (NPs), which are detectable with MRI for in vivo tracking, to detect stem cell proliferation using the Oct4 receptor as a marker of stem cells. In the first phase, iron NPs were fabricated, and their successful synthesis was confirmed using FTIR spectroscopy. Next, the Alexa Fluor anti-Oct4 antibody was conjugated with as-synthesized NPs. Their affinity to the cell surface marker in fresh and saltwater conditions was confirmed using two types of cells, murine mesenchymal stromal/stem cell culture and sea anemone stem cells. For this purpose, 106 cells of each type were exposed to NP-conjugated antibodies and their affinity to antibodies was confirmed by an epi-fluorescent microscope. The presence of iron-NPs imaged with the light microscope was confirmed by iron staining using Prussian blue stain. Next, anti-Oct4 antibodies conjugated with iron NPs were injected into a brittle star, and proliferating cells were tracked by MRI. To sum up, anti-Oct4 antibodies conjugated with iron NPs not only have the potential for identifying proliferating stem cells in different cell culture conditions of sea anemone and mouse cell cultures but also has the potential to be used for in vivo MRI tracking of marine proliferating cells.
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Nanopartículas de Magnetita , Nanopartículas , Humanos , Camundongos , Animais , Ferro , Medicina Regenerativa , Anticorpos , Imageamento por Ressonância Magnética/métodos , Nanopartículas de Magnetita/químicaRESUMO
OBJECTIVE: Recently, the decellularization technique is introduced as one of the tissue engineering procedures for the treatment of various deficiencies. Here, we aimed to assess the dynamic activity of CCs and HUVECs within decellularized bovine ovarian tissue transplanted subcutaneously in rats. Ovarian tissue was decellularized using a cocktail consisting of different chemicals, and the efficiency of decellularization was assessed using hematoxylin-eosin and DAPI staining. The cell survival was evaluated using an LDH leakage assay. Thereafter, decellularized samples were recellularized using HUVECs and CCs, encapsulated inside alginate (1.2%)-gelatin, (1%) hydrogel, and transplanted subcutaneously to rats. The existence of CD31- and estrogen-positive cells was assessed using immunohistochemistry staining. RESULTS: Bright-field imaging and DAPI staining revealed the lack of nuclei with naive matrix structure in ovarian tissue subjected to decellularization protocol. SEM imaging revealed a normal matrix in decellularized ovaries. LDH assay showed a lack of cytotoxicity for CCs after 7-days compared to the control group. Immunohistochemistry staining showed both CD31- and estrogen-positive cells in CCs + HUVECs compared to the CCs group. CD31 cells appeared with flattened morphology aligned with matrix fibers. The existence of estrogen and CD31 positive cells showed the efficiency of decellularized ovarian tissue to restore cellular function and activity.
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Células Endoteliais , Matriz Extracelular , Feminino , Ratos , Bovinos , Animais , Engenharia Tecidual/métodos , Ovário , EstrogêniosRESUMO
Bioactive glasses are a group of bioceramic materials that have extensive clinical applications. Their properties such as high biocompatibility, antimicrobial features, and bioactivity in the internal environment of the body have made them useful biomaterials in various fields of medicine and dentistry. There is a great variation in the main composition of these glasses and some of them whose medical usage has been approved by the US Food and Drug Administration (FDA) are called Bioglass. Bioactive glasses have appropriate biocompatibility with the body and they are similar to bone hydroxyapatite in terms of calcium and phosphate contents. Bioactive glasses are applied in different branches of dentistry like periodontics, orthodontics, endodontics, oral and maxillofacial surgery, esthetic and restorative dentistry. Also, some dental and oral care products have bioactive glasses in their compositions. Bioactive glasses have been used as dental implants in the human body in order to repair and replace damaged bones. Other applications of bioactive glasses in dentistry include their usage in periodontal disease, root canal treatments, maxillofacial surgeries, dental restorations, air abrasions, dental adhesives, enamel remineralization, and dentin hypersensitivity. Since the use of bioactive glasses in dentistry is widespread, there is a need to find methods and extensive resources to supply the required bioactive glasses. Various techniques have been identified for the production of bioactive glasses, and marine sponges have recently been considered as a rich source of it. Marine sponges are widely available and many species have been identified around the world, including the Persian Gulf. Marine sponges, as the simplest group of animals, produce different bioactive compounds that are used in a wide range of medical sciences. Numerous studies have shown the anti-tumor, anti-viral, anti-inflammatory, and antibiotic effects of these compounds. Furthermore, some species of marine sponges due to the mineral contents of their structural skeletons, which are made of biosilica, have been used for extracting bioactive glasses.
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Some studies have demonstrated that stroke may increase the risk of pregnancy complications and early menopause. In addition, preclinical investigations revealed the middle cerebral artery occlusion could affect hypothalamus. Since hypothalamus is the core of central circuits regulating reproductive processes, impairment of hypothalamic gonadotropin-releasing hormone neuronal network following stroke might be manifested in long-lasting reproductive disorders.
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Hormônio Liberador de Gonadotropina , Acidente Vascular Cerebral , Feminino , Hormônio Liberador de Gonadotropina/metabolismo , Humanos , Hipotálamo/metabolismo , Neurônios/metabolismo , Gravidez , Reprodução/fisiologia , Acidente Vascular Cerebral/complicaçõesRESUMO
Lung cancer is one of the most common and lethal cancers in human beings. Lung cancer has been divided into two major types: small cell lung cancer (SCLC) and non-small cell lung carcinoma (NSCLC). Current drugs suffer from various side effects, and the insufficient efficacy of present treatments creates a desire for better more efficient new drugs. This review compares the diversity of marine-derived bioactive compounds from different marine species. Some of the natural products from marine resources are in different stages of clinical trials. By the way, most of them have been studied in vitro and in vivo. Additionally, in this review, the mechanisms of action of marine-derived anti-lung cancer components on lung cancer cell lines have been reviewed. In addition, considering growing rate and the high costs of cancer research, attention must be paid to some aspects of targeting and developing anti-lung cancer drug. In better words, like the other therapeutic strategies that have their particular challenges and weak points, several challenges about marine-derived anti-lung cancer components which exist for scientists for doing research are explained. Moreover, as the attentions in the field of cancer therapy are focused on designing and developing new anticancer strategies for the treatment of cancer in the future, the application of marine-derived anti-lung cancer components in the field of future cancer therapy and their role in future anticancer strategies are briefly discussed.
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Antineoplásicos , Produtos Biológicos , Neoplasias Pulmonares , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Organismos Aquáticos , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Humanos , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
Polycystic ovary syndrome (PCOS) is a common endocrinopathy in women. PCOS is characterized by anovulation, hyperandrogenism, polycystic ovaries, insulin resistance, and obesity. Despite the finding that the genetic origin of PCOS is well demonstrated in previous twin and familial clustering studies, genes and factors that can exactly explain the PCOS pathophysiology are not known. Objective(s). In this review, we attempted to identify genes related to secretion and signaling of insulin aspects of PCOS and their physiological functions in order to explain the pathways that are regulated by these genes which can be a prominent function in PCOS predisposition. Materials and Methods. For this purpose, published articles and reviews dealing with genetic evaluation of PCOS in women from peer-reviewed journals in PubMed and Google Scholar databases were included in this review. Results. The genomic investigations in women of different populations identified many candidate genes and loci that are associated with PCOS. The most important of them are INSR, IRS1-2, MTNR1A, MTNR1B, THADA, PPAR-γ2, ADIPOQ, and CAPN10. These are mainly associated with metabolic aspects of PCOS. Conclusions. In this review, we proposed that each of these genes may interrupt specific physiological pathways by affecting them and contribute to PCOS initiation. It is clear that the role of genes involved in insulin secretion and signaling is more critical than other pathways.
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Hiperandrogenismo , Resistência à Insulina , Síndrome do Ovário Policístico , Feminino , Predisposição Genética para Doença/genética , Humanos , Resistência à Insulina/genética , Secreção de Insulina/genética , Síndrome do Ovário Policístico/genéticaRESUMO
An automatic decellularization device was developed to perfuse and decellularize male rats' kidneys using both sodium lauryl ether sulfate (SLES) and sodium dodecyl sulfate (SDS) and to compare their efficacy in kidney decellularization and post-transplantation angiogenesis. Kidneys were perfused with either 1% SDS solution for 4 h or 1% SLES solution for 6 h. The decellularized scaffolds were stained with hematoxylin and eosin, periodic acid Schiff, Masson's trichrome, and Alcian blue to determine cell removal and glycogen, collagen, and glycosaminoglycan contents, respectively. Moreover, scanning electron microscopy was performed to evaluate the cell removal and preservation of microarchitecture of both SDS and SLES scaffolds. Additionally, DNA quantification assay was applied for all groups in order to measure residual DNA in the scaffolds and normal kidney. In order to demonstrate biocompatibility of the decellularized scaffolds, human umbilical cord mesenchymal stromal/stem cells (hUC-MSCs) were seeded on the scaffolds. In addition, the allotransplantation was performed in back muscle and angiogenesis was evaluated. Complete cell removal in both SLES and SDS groups was observed in scanning electron microscopy and DNA quantification assays. Moreover, the extracellular matrix (ECM) architecture of rat kidney in the SLES group was significantly preserved better than the SDS group. The hUC-MSCs were successfully migrated from the cell culture plate surface into the SDS and SLES decellularized scaffolds. The formation of blood vessels was observed in the kidney in both SLES and SDS decellularized kidneys. The better preservation of ECM than SDS introduces SLES as the solvent of choice for kidney decellularization.
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Matriz Extracelular Descelularizada/química , Rim/química , Polietilenoglicóis/química , Dodecilsulfato de Sódio/química , Alicerces Teciduais/química , Animais , Rim/citologia , Rim/ultraestrutura , Ratos , Ratos Sprague-Dawley , Transplante de Células-Tronco , Células-Tronco/citologia , Engenharia TecidualRESUMO
BACKGROUND: Stressful conditions increase alcohol consumption in men. Clinical studies link disruption of the neuroendocrine stress system with alcoholism, but the effect of alcohol in a stress condition on male fertility is still relatively poorly understood. This project was undertaken to evaluate the effect of sub-chronic alcohol in a stress condition on male fertility in a rat model. METHODS: Male Sprague-Dawley rats were randomly divided into a control group, a stress group that was exposed to restraint stress, an ethanol group that was injected with ethanol daily, and a stress + ethanol group that was injected with ethanol daily and was exposed to restraint stress, simultaneously. Furthermore, testis tissue was evaluated histomorphometrically and immunohistochemically for apoptosis using a TUNEL assay after 12 days. Epididymis sperm analysis was done. Blood cortisol and testosterone were measured and expression of hypothalamic kisspeptin (Kiss1), RFRP-3, and MC4R mRNA were evaluated. RESULTS: Ethanol exposure during restraint stress did not alter body weight. Ethanol exposure decreased the cellular diameter and area, and stress increased the cellular diameter and area, in comparison with the control group. In the stress group, in comparison with the other groups, the number of seminiferous tubules decreased and the numerical density of seminiferous tubules increased. In addition, ethanol exposure and/or stress reduced semen analysis parameters (sperm viability and motility), but did not change serum testosterone concentrations. Apoptosis increased in spermatogonia with ethanol exposure, but spermatocytes were not affected. Our data present the novel finding that ethanol and stress reduced hypothalamic Kiss1 mRNA expression, while ethanol exposure decreased hypothalamic RFRP-3 and MC4R mRNA expression. CONCLUSIONS: Ethanol decreased cortisol hormone level during the restraint stress condition and attenuated hypothalamic reproductive-related gene expressions. Therefore, ethanol exposure may induce reduction of sperm viability, increased sperm mortality, and increased apoptosis, with long-term effects, and may induce permanent male subfertility.
Assuntos
Etanol , Infertilidade Masculina , Estresse Psicológico , Testículo , Animais , Apoptose , Etanol/toxicidade , Infertilidade Masculina/induzido quimicamente , Kisspeptinas , Masculino , Ratos , Ratos Sprague-Dawley , Receptor Tipo 4 de Melanocortina , Motilidade dos Espermatozoides , Espermatogênese , TestosteronaRESUMO
Uterine fibrosis is an acquired disorder leading to menstrual irregularities, implantation impairment, and abortion. Mesenchymal stromal cells (MSCs) have antifibrotic properties through chemokine secretion. MSC-conditioned media (MSC-CM) contain paracrine components-exosomes-with a great potential for repairing damaged tissue or preventing fibrosis. The main goal of this study was to evaluate the preventive effects of bone marrow-derived MSC-CM (BM-MSC-CM) on uterine fibrosis after uterine curettage in rabbits. This study included 12 female rabbits (24 uterine horns in total). Excised uteri of each of the 12 female rabbits were randomly divided into four groups of intact negative control, curettage positive control, BM-MSC injection, and BM-MSC-CM injection in the way that two corresponding uteri from a rabbit were allocated to different groups. The MSC-CM were collected from cultivated BM-MSCs 48 hours after having been washed three times and replaced in serum-free media. Through a surgical approach, the caudal parts of the uteri were submitted to traumatic endometrial curettage, except for the intact negative uteri. After suturing the uterine walls, BM-MSCs or BM-MSC-CM were injected in the curettage site. Endometrial regeneration was histologically evaluated 30 days after treatment. Based on the evaluation of histomorphometric indices, curettage with or without preventive injections increased the growth of endometrial layers. However, the amount of fibrotic tissue in the CM and the BM-MSC injection groups was the same as the normal control groups, and all were less than the curettage group. A single injection of CM of MSCs after 30 days prevented the fibrotic tissue formation induced by curettage in endometrial layers of rabbits. Injecting BM-MSC-CM immediately after curettage prevented and reduced the uterine fibrosis similar to BM-MSCs in a rabbit model.