RESUMO
Propolis is a natural product used in cancer treatment, which is produced by bees via different sources. The chemical composition of Propolis is determined based on the climatic and geographical conditions, as well as harvesting time and method. This compound has been the subject of numerous investigational endeavors due to its expansive therapeutic capacity which includes antibacterial, anti-fungal, anti-inflammatory, anti-oxidant, anti-viral, and anti-cancer effects. The growing incidence rate of different cancers necessitates the need for developing novel preventive and therapeutic strategies. Chemotherapy, radiotherapy, and stem cell therapy have proved effective in cancer treatment, regardless of the adverse events associated with these modalities. Clinical application of natural compounds such as Propolis may confer promise as an adjuvant therapeutic intervention, particularly in certain subpopulations of patients that develop adverse events associated with anticancer regimens. The diverse biologically active compounds of propolis are believed to confer anti-cancer potential by modulation of critical signaling cascades such as caffeic acid phenethyl ester, Galangin, Artepillin C, Chrysin, Quercetin, Caffeic acid, Nymphaeols A and C, Frondoside A, Genistein, p-coumaric acid, and Propolin C. This review article aims to deliver a mechanistic account of anti-cancer effects of propolis and its components. Propolis can prevent angiogenesis by downregulating pathways involving Jun-N terminal kinase, ERK1/2, Akt and NF-ÆB, while counteracting metastatic progression of cancer by inhibiting Wtn2 and FAK, and MAPK and PI3K/AKT signaling pathways. Moreover, propolis or its main components show regulatory effects on cyclin D, CDK2/4/6, and their inhibitors. Additionally, propolis-induced up-regulation of p21 and p27 may result in cell cycle arrest at G2/M or G0/G1. The broad anti-apoptotic effects of propolis are mediated through upregulation of TRAIL, Bax, p53, and downregulation of the ERK1/2 signaling pathway. Considering the growing body of evidence regarding different anti-cancers effects of propolis and its active components, this natural compound could be considered an effective adjuvant therapy aimed at reducing related side effects associated with chemotherapy and radiotherapy.
Assuntos
Neoplasias , Própole , Transdução de Sinais , Própole/farmacologia , Própole/química , Própole/uso terapêutico , Humanos , Transdução de Sinais/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Ácidos Cafeicos/farmacologia , Ácidos Cafeicos/uso terapêutico , Ácidos Cafeicos/química , Álcool Feniletílico/análogos & derivados , FenilpropionatosRESUMO
INTRODUCTION: Bacterial infections and the rising antimicrobial resistance pose a significant threat to public health. Pseudomonas aeruginosa produces bacteriocins like pyocins, especially S-type pyocins, which are promising for biological applications. This research focuses on clinical P. aeruginosa isolates to assess their bacteriocin production, inhibitory spectrum, chemical structure, antibacterial agents, and preservative potential. METHODS: The identification of P. aeruginosa was conducted through both phenotypic and molecular approaches. The inhibitory spectrum and antibacterial potential of the isolates were assessed. The kinetics of antibacterial peptide production were investigated, and the activity of bacteriocin was quantified in arbitrary units (AU ml-1). Physico-chemical characterization of the antibacterial peptides was performed. Molecular weight estimation was carried out using SDS-PAGE. qRT-PCR analysis was employed to validate the expression of the selected candidate gene. RESULT: The antibacterial activity of P. aeruginosa was attributed to the secretion of bacteriocin compounds, which belong to the S-type pyocin family. The use of mitomycin C led to a significant 65.74% increase in pyocin production by these isolates. These S-type pyocins exhibited the ability to inhibit the growth of both Gram-negative (P. mirabilis and P. vulgaris) and Gram-positive (S. aureus, S. epidermidis, E. hirae, S. pyogenes, and S. mutans) bacteria. The molecular weight of S-type pyocin was 66 kDa, and its gene expression was confirmed through qRT-PCR. CONCLUSION: These findings suggest that S-type pyocin hold significant potential as therapeutic agents against pathogenic strains. The Physico-chemical resistance of S-type pyocin underscores its potential for broad applications in the pharmaceutical, hygiene, and food industries.
Assuntos
Antibacterianos , Bacteriocinas , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa , Pseudomonas aeruginosa/metabolismo , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/genética , Antibacterianos/farmacologia , Antibacterianos/biossíntese , Bacteriocinas/biossíntese , Bacteriocinas/farmacologia , Bacteriocinas/metabolismo , Piocinas/metabolismo , Piocinas/farmacologia , Piocinas/biossíntese , Humanos , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/tratamento farmacológicoRESUMO
The interplay between gut microbiota and human health, both mental and physical, is well-documented. This connection extends to the gut-brain-skin axis, linking gut microbiota to skin health. Recent studies have underscored the potential of probiotics and prebiotics to modulate gut microbiota, supported by in vivo and clinical investigations. In this comprehensive review, we explore the immunological implications of probiotics in influencing the gut-skin axis for the treatment and prevention of skin conditions, including psoriasis, acne, diabetic ulcers, atopic dermatitis, and skin cancer. Our analysis reveals that probiotics exert their effects by modulating cytokine production, whether administered orally or topically. Probiotics bolster skin defenses through the production of antimicrobial peptides and the induction of keratinocyte differentiation and regeneration. Yet, many questions surrounding probiotics remain unanswered, necessitating further exploration of their mechanisms of action in the context of skin diseases.
Assuntos
Probióticos , Dermatopatias , Humanos , Probióticos/uso terapêutico , Pele , Prebióticos , Dermatopatias/terapia , EncéfaloRESUMO
Objectives: This study aimed to evaluate the effects of voluntary exercise as an anti-inflammatory intervention on the pulmonary levels of inflammatory cytokines in type 2 diabetic male rats. Materials and Methods: Twenty-eight male Wistar rats were divided into four groups (n=7), including control (Col), diabetic (Dia), voluntary exercise (Exe), and diabetic with voluntary exercise (Dia+Exe). Diabetes was induced by a high-fat diet (4 weeks) and intraperitoneal injection of streptozotocin (35 mg/kg), and animals did training on the running wheel for 10 weeks as voluntary exercise. Finally, the rats were euthanized and the lung tissues were sampled for the evaluation of the levels of pulmonary interleukin (IL)-10, IL-11, and TNF-α using ELISA, and the protein levels of Nrf-2 and NF-κB using western blotting and tissue histopathological analysis. Results: Diabetes reduced the IL-10, IL-11, and Nrf2 levels (P<0.001 to P<0.01) and increased the levels of TNF-α and NF-κB compared to the Col group (P<0.001). Lung tissue levels of IL-10, IL-11, and Nrf2 in the Dia+Exe group enhanced compared to the Dia group (P<0.001 to P<0.05), however; the TNF-α and NF-κB levels decreased (P<0.001). The level of pulmonary Nrf2 in the Dia+Exe group was lower than that of the Exe group while the NF-κB level increased (P<0.001). Moreover, diabetes caused histopathological changes in lung tissue which improved with exercise in the Dia+Exe group. Conclusion: These findings showed that voluntary exercise could improve diabetes-induced pulmonary complications by ameliorating inflammatory conditions.
RESUMO
BACKGROUND: Breast cancer (BC) is the most prevalent cancer in women, with increasing incidence and death rates in recent years. Disruptions of different signaling pathways partially cause breast cancer. Hence, different genes through particular pathways are involved in BC tumorigenesis. METHODS: In this study, we evaluated the expression level of GLIS2 and CCND1 genes in 50 patients. Also, in-silico analyses were used to enrich related signaling pathways involving the mentioned genes. RESULTS: The results showed an increased expression level of Cyclin D1 and decreased expression level of GLIS2 in BC patients. Moreover, a relationship between aberrant expression levels of GLIS2 and CCND1 and BC development was determined. CONCLUSION: These observations could help uncover new therapeutic targets for treating patients with BC in the progressive stage.
Assuntos
Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/metabolismo , Ciclina D1/genética , Ciclina D1/metabolismo , Amplificação de GenesRESUMO
BACKGROUND: The physiological level of reactive oxygen species (ROS) is necessary for many cellular functions. However, during the in-vitro manipulations, cells face a high level of ROS, leading to reduced cell quality. Preventing this abnormal ROS level is a challenging task. Hence, here we evaluated the effect of sodium selenite supplementation on the antioxidant potential, stemness capacity, and differentiation of rat-derived Bone Marrow MSCs (rBM-MSCs) and planned to check our hypothesis on the molecular pathways and networks linked to sodium selenite's antioxidant properties. METHODS: MTT assay was used to assess the rBM-MSCs cells' viability following sodium selenite supplementation (concentrations of: 0.001, 0.01, 0.1, 1, 10 µM). The expression level of OCT-4, NANOG, and SIRT1 was explored using qPCR. The adipocyte differentiation capacity of MSCs was checked after Sodium Selenite treatment. The DCFH-DA assay was used to determine intracellular ROS levels. Sodium selenite-related expression of HIF-1α, GPX, SOD, TrxR, p-AKT, Nrf2, and p38 markers was determined using western blot. Significant findings were investigated by the String tool to picture the probable molecular network. RESULTS: Media supplemented with 0.1 µM sodium selenite helped to preserve rBM-MSCs multipotency and keep their surface markers presentation; this also reduced the ROS level and improved the rBM-MSCs' antioxidant and stemness capacity. We observed enhanced viability and reduced senescence for rBM-MSCs. Moreover, sodium selenite helped in rBM-MSCs cytoprotection by regulating the expression of HIF-1 of AKT, Nrf2, SOD, GPX, and TrxR markers. CONCLUSIONS: We showed that sodium selenite could help protect MSCs during in-vitro manipulations, probably via the Nrf2 pathway.
Assuntos
Células-Tronco Mesenquimais , Selenito de Sódio , Ratos , Animais , Selenito de Sódio/farmacologia , Selenito de Sódio/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células Cultivadas , Estresse Oxidativo , Transdução de Sinais , Diferenciação Celular , Superóxido Dismutase/metabolismoRESUMO
Utilizing both medium enrichment and a thermos-responsive substrate to maintain the cell-to-cell junctions and extracellular matrix (ECM) intact, cell sheet technology has emerged as a ground-breaking approach. Investigating the possibility of using sodium selenite (as medium supplementation) and PCL-PEG-PCL (as vessel coating substrate) in the formation of the sheets from rat bone marrow-derived mesenchymal stem cells (rBMSCs) was the main goal of the present study. To this end, first, Polycaprolactone-co-Poly (ethylene glycol)-co-Polycaprolactone triblock copolymer (PCEC) was prepared by ring-opening copolymerization method and characterized by FTIR, 1 H NMR, and GPC. The sol-gel-sol phase transition temperature of the PCEC aqueous solutions with various concentrations was either measured. Next, rBMSCs were cultured on the PCEC, and let be expanded in five different media containing vitamin C (50 µg/ml), sodium selenite (0.1 µM), vitamin C and sodium selenite (50 µg/ml + 0.1 µM), Trolox, and routine medium. The proliferation of the cells exposed to each material was evaluated. Produced cell sheets were harvested from the polymer surface by temperature reduction and phenotypically analyzed via an inverted microscope, hematoxylin and eosin (H&E) staining, and field emission scanning electron microscopy (FESEM). Through the molecular level, the expression of the stemness-related genes (Sox2, Oct-4, Nanog), selenium-dependent enzymes (TRX, GPX-1), and aging regulator gene (Sirt1) were measured by q RT-PCR. Senescence in cell sheets was checked by beta-galactosidase assay. The results declared the improved ability of the rBMSCs for osteogenesis and adipogenesis in the presence of antioxidants vitamin C, sodium selenite, and Trolox in growth media. The data indicated that in the presence of vitamin C and sodium selenite, the quality of the cell sheet was risen by reducing the number of senescent cells and high transcription of the stemness genes. Monolayers produced by sodium selenite was in higher-quality than the ones produced by vitamin C.
RESUMO
Exosomes are nanosized extracellular vesicles secreted by nearly all viable cells following the fusing of multivesicular bodies and the plasma membrane and discharged into the encircling bodily fluids. Exosomes can transport cell-specific components from the source cell to the target cell. Given the enormous potential of exosomes as non-invasive diagnostic biomarkers and therapeutic nanovehicles. Lately, accumulated evidence has demonstrated that exosomes serve an important role in prognosis, diagnosis, and even treatment strategies. While several reviews have collective information on the biomedical application of exosomes, a comprehensive review incorporating updated and improved methodologies for beneficial applications of such vesicles in cancer theranostics is indispensable. In the current review, we first provided a comprehensive review of the introduction of exosomes, featuring their discovery, separation, characterization, function, biogenesis, secretion. The implications of exosomes as promising nanovehicles for drug and gene delivery, application of exosome inhibitors in the management of cancers, completed and ongoing clinical trials on the biological relevance of exosomes are then discussed in detail. As the field of exosome research grows, a better understanding of the subcellular parts and mechanisms involved in exosome secretion and targeting of specific cells will help figure out what their exact physiological functions are in the body.
Assuntos
Exossomos , Vesículas Extracelulares , Neoplasias , Humanos , Transporte Biológico , Exossomos/metabolismo , Vesículas Extracelulares/metabolismo , Neoplasias/diagnóstico , Neoplasias/terapia , Neoplasias/metabolismo , Medicina de Precisão , Ensaios Clínicos como AssuntoRESUMO
OBJECTIVES: Investigation the association of pro-inflammatory markers interleukin (IL)-1ß and IL- 10 expression, serum levels of C-reactive protein (CRP), cyclooxygenase-2 (COX2), High-density lipoprotein (HDL), Apolipoprotein A1 (ApoA1), and ATP Binding Cassette Subfamily A Member 1 (ABCA1) inflammatory proteins with atherosclerosis index (homocysteine) in normal-weight and obese male subjects. METHODS: 59 males including 30 obese (Body mass index (BMI) of ≥30 kg/m2) and 29 normal-weight (BMI of 18.5-24.9 kg/m2) were joined to this study. Plasma levels of IL-1ß and IL-10 (pg/mL), CRP (pg/mL), COX-2 (ng/mL), APOA1 (mg/dL), ABCA1 (ng/mL), HDL, Cholesterol, and Triglyceride (TG) (mg/dL), and homocysteine (µmol/L) was measured. Association of these biomarkers with homocysteine was determined. RESULTS: Obese subjects had higher serum levels of IL10, IL1ß, CRP, COX-2, TG, and cholesterol concentrations (all p<0.05 except IL-10 and cholesterol) and low levels of HDL, APOA1, and ABCA1 (non-significant differences) in comparison to normal-weight group. Homocysteine levels were high in obese men with no significant differences between the two groups. In obese subjects, homocysteine had a significant inverse correlation with APOA1, ABCA1, and HDL, and a strong and moderate positive correlation was found with CRP and TG levels, respectively. CONCLUSIONS: High level of homocysteine and its correlation with inflammation proteins and markers in obese subjects appear to be contributed with atherosclerosis development.
Assuntos
Aterosclerose , Citocinas , Humanos , Masculino , Interleucina-10 , Ciclo-Oxigenase 2 , Obesidade/complicações , Colesterol , Triglicerídeos , Lipoproteínas HDL , Proteína C-Reativa/análise , Aterosclerose/etiologiaRESUMO
Nervous system disorders are one of the common problems that affect many people around the world every year. Regarding the beneficial effects of the probiotics on the gut and the gut-brain axis, their application along with current medications has been the subject of intense interest. Psychobiotics are a probiotic strain capable to affect the gut-brain axis. The effective role of Psychobiotics in several neurological disorders is documented. Consumption of the Psychobiotics containing nutrients has positive effects on the improvement of microbiota as well as alleviation of some symptoms of central nervous system (CNS) disorders. In the present study, the effects of probiotic strains on some CNS disorders in terms of controlling the disease symptoms were reviewed. Finding suggests that Psychobiotics can efficiently alleviate the symptoms of several CNS disorders such as autism spectrum disorders, Parkinson's disease, multiple sclerosis, insomnia, depression, diabetic neuropathy, and anorexia nervosa. It can be concluded that functional foods containing psychotropic strains can help to improve mental health.
Assuntos
Doenças do Sistema Nervoso Central , Microbioma Gastrointestinal , Microbiota , Probióticos , Encéfalo , Eixo Encéfalo-Intestino , Humanos , Microbiota/fisiologia , Probióticos/farmacologia , Probióticos/uso terapêuticoRESUMO
Objective: Nephropathy is known to be the leading cause of kidney failure in diabetic patients. Troxerutin, as a flavonoid component, could provide a novel protective strategy in the prevention of diabetic nephropathy. A large number of reports on the salutary effects of troxerutin inspired us to investigate its effect on the nephropathy signaling events (i.e., expression of TGF-ß, miRNA192, and SIP1) in type-1 induced diabetic rats. Materials and Methods: 50 male Wistar rats were divided into 5 groups including control group, sham group treated with troxerutin for 4 weeks, diabetic group induced by streptozotocin (STZ) injection, DI group including insulin-treated diabetic animals and DT group treated with troxerutin. Ultimately, rat kidneys were extracted, and the level of miR-192 (using qPCR), transforming growth factor-beta (TGF-ß), and smad interacting protein 1 (SIP1) using an ELISA kit, was measured. Results: The level of TGF-ß and miRNA192 significantly increased in the diabetic group. However, their expression levels decreased following the administration of troxerutin and insulin (p<0.05) compared to control group. SIP1 was down-regulated in the diabetic group, whereas a spike in the expression levels was observed after troxerutin administration compared to control and troxerutin groups (p<0.05). However, no significant difference was found in the effects of insulin and troxerutin on the level of miR-192, SIP1, and TGF- ß. Conclusion: According to the previous literatures, during the progression of nephropathy, TGF-ß represses SIP1 (the repression region in the collagen gene) by increasing the expression of miR-192. Ultimately, in this study, diabetes led to up-regulation of TGF-ß while troxerutin proved to have a protective effect on the kidney by increasing SIP and lowering miR-192 levels.
RESUMO
Background and Aims: All components of the immune system are involved in alleviating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Further research is required to provide detailed insights into COVID-19-related immune compartments and pathways. In addition, a significant percentage of hospitalized COVID-19 patients suspect bacterial infections and antimicrobial resistance occurs following antibiotics treatment. The aim of this study was to evaluate the possible effects of antibiotics on the response of neutrophil-related genes in SARS-CoV-2 patients by an experimental in silico study. Methods: The two data sets GSE1739 and GSE21802 including 10 SARS positive patients and 35 influenza A (H1N1) patients were analyzed, respectively. Differentially expressed genes (DEGs) between these two data sets were determined by GEO2R analysis and the Venn diagram online tool. After determining the hub genes involved in immune responses, the expression of these genes in 30 COVID-19 patients and 30 healthy individuals was analyzed by real-time polymerase chain reaction (PCR). All patients received antibiotics, including levofloxacin, colistin, meropenem, and ceftazidime. Results: GEO2R analysis detected 240 and 120 DEGs in GSE21802 and GSE1739, respectively. Twenty DEGs were considered as enriched hub genes involved in immune processes such as neutrophil degranulation, neutrophil activation, and antimicrobial humoral response. The central nodes were attributed to the genes of neutrophil elastase (ELANE), arginase 1 (ARG-1), lipocalin 2 (LCN2), and defensin 4 (DEFA4). Compared to the healthy subjects, the expression of LCN2 and DEFA4 were significantly reduced in COVID-19 patients. However, no significant differences were observed in the ELANE and AGR-1 levels between COVID-19 subjects and the control group. Conclusions: Activation and degranulation of neutrophils were observed mainly in SARS, and H1N1 infection processes and antibiotics administration could affect neutrophil activity during viral infection. It can be suggested that antibiotics can decrease inflammation by restoring the expression of neutrophil-related genes in COVID-19 patients.
RESUMO
OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the novel coronavirus causing severe respiratory illness (COVID-19). This virus was initially identified in Wuhan city, a populated area of the Hubei province in China, and still remains one of the major global health challenges. RNA interference (RNAi) is a mechanism of post-transcriptional gene silencing that plays a crucial role in innate viral defense mechanisms by inhibiting the virus replication as well as expression of various viral proteins. Dicer, Drosha, Ago2, and DGCR8 are essential components of the RNAi system, which is supposed to be dysregulated in COVID-19 patients. This study aimed to assess the expression level of the mentioned mRNAs in COVID-19patients compared to healthy individuals. RESULTS: Our findings demonstrated that the expression of Dicer, Drosha, and Ago2 was statistically altered in COVID-19 patients compared to healthy subjects. Ultimately, the RNA interference mechanism as a crucial antiviral defense system was suggested to be dysregulated in COVID-19 patients.
Assuntos
COVID-19 , MicroRNAs , Humanos , Interferência de RNA , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , SARS-CoV-2RESUMO
Development of novel technologies provides the best tissue constructs engineering and maximizes their therapeutic effects in regenerative therapy, especially for liver dysfunctions. Among the currently investigated approaches of tissue engineering, scaffold-based and scaffold-free tissues are widely suggested for liver regeneration. Analogs of liver acellular extracellular matrix (ECM) are utilized in native scaffolds to increase the self-repair and healing ability of organs. Native ECM analog could improve liver repairing through providing the supportive framework for cells and signaling molecules, exerting normal biomechanical, biochemical, and physiological signal complexes. Recently, innovative cell sheet technology is introduced as an alternative for conventional tissue engineering with the advantage of fewer scaffold restrictions and cell culture on a Thermo-Responsive Polymer Surface. These sheets release the layered cells through a temperature-controlled procedure without enzymatic digestion, while preserving the cell-ECM contacts and adhesive molecules on cell-cell junctions. In addition, several novelties have been introduced into the cell sheet and decellularization technologies to aid cell growth, instruct differentiation/angiogenesis, and promote cell migration. In this review, recent trends, advancements, and issues linked to translation into clinical practice are dissected and compared regarding the decellularization and cell sheet technologies for liver tissue engineering.
Assuntos
Matriz Extracelular/química , Hepatopatias/terapia , Regeneração Hepática , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Animais , HumanosRESUMO
PURPOSE: Liver tissue engineering via cell sheet technology would open new doors for treatment of patients with liver failure. Decellularized tissues could provide sufficient extracellular matrix (ECM) to support development of hepatocytes in in vivo niches. Besides, with the potential of temperature responsive polymer (pNIPAAm) as an intelligent surface for controlling the attachment/detachment of cell, we set out to generate three in vitro microenvironments models including I: pNIPAAm hydrogel (pN hydrogel), II: decellularized ECM incorporated into pNIPAAm hydrogel (dECM + pN hydrogel) and III: decellularized ECM scaffold (dECM scaffold) to investigate the structural and function cues of hepatocyte-like cells after differentiation of adipose tissue-derived mesenchymal stem cells (AT-MSCs) on the surface of these models. METHOD: dECM scaffold was obtained after decellularization of rat liver, and its efficiency was analyzed. pN hydrogel and dECM + pN hydrogel (1:3 and 2:3 ratios) of were fabricated, and scaffold architecture was characterized. Each well of culturing plates was coated separately with these three constructs and AT-MSCs were instructed to differentiate into hepatocyte-like cells (HLCs). After recellularization, patterns of differentiation, and expression of hepatogenic markers were investigated via biochemical assays and qRT-PCR at different time points. RESULTS: Multipotency of AT-MSCs, after their ability for osteogenesis and adipogenesis was documented. Production of dense and intact cell sheets was reported in dECM + pN hydrogel, as opposed to pN hydrogel and dECM scaffold. Also, statistically significant difference of HLCs functionality in dECM + pN hydrogel was confirmed after evaluation of the expression of hepatocyte markers including, alpha-fetoprotein, cytokeratin 18, cytochrome P450-2E1 and phosphoenolpyruvate carboxykinase. CONCLUSION: Our results proved dECM + pN hydrogel were able to preserve hepatocyte function in cell sheets owing to the high level of albumin, urea, hepatogenic markers, and glycogenesis potential of HLCs. Accordingly, dECM incorporated in pN hydrogel could remodel microenvironments to guide the AT-MSCs into conducive differentiation and proliferation to give rise to multilayer sheets of cells in their own ECM.
Assuntos
Matriz Extracelular/química , Hepatócitos/metabolismo , Células-Tronco Mesenquimais/química , Polímeros/química , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Adipogenia , Animais , Biomarcadores , Diferenciação Celular , Proliferação de Células , Hepatócitos/química , Humanos , Hidrogéis/química , Falência Hepática/terapia , Masculino , Células-Tronco Mesenquimais/metabolismo , Osteogênese , Ratos , Ratos WistarRESUMO
Background The global trend of obesity and diabetes is considerable. Recently, the early diagnosis and accurate prediction of type 2 diabetes mellitus (T2DM) patients have been planned to be estimated according to precise and reliable methods, artificial networks and machine learning (ML). Materials and methods In this study, an experimental data set of relevant features (adipocytokines and anthropometric levels) obtained from obese women (diabetic and non-diabetic) was analyzed. Machine learning was used to select significant features [by the separability-correlation measure (SCM) algorithm] for classification of women with the best accuracy and the results were evaluated using an artificial neural network (ANN). Results According to the experimental data analysis, a significant difference (p < 0.05) was found between fasting blood sugar (FBS), hemoglobin A1c (HbA1c) and visfatin level in two groups. Moreover, significant correlations were determined between HbA1c and FBS, homeostatic model assessment (HOMA) and insulin, total cholesterol (TC) level and body mass index (BMI) in non-diabetic women and insulin and HOMA, FBS and HbA1c, insulin and HOMA, systolic blood pressure (SBP) and diastolic blood pressure (DBP), BMI and TC and HbA1c and TC in the diabetic group. Furthermore, there were significant positive correlations between adipocytokines except for the resistin and leptin levels for both groups. The excellent (FBS and HbA1c), good (HOMA) and fair (visfatin, adiponectin and insulin) discriminators of diabetic women were determined based on specificities and sensitivities level. The more selected features in the ML method were FBS, apelin, visfatin, TC, HbA1c and adiponectin. Conclusions Thus, the subset of features involving FBS, apelin, visfatin and HbA1c are significant features and make the best discrimination between groups. In this study, based on statistical and ML results, the useful biomarkers for discrimination of diabetic women were FBS, HbA1c, HOMA, insulin, visfatin, adiponectin and apelin. Eventually, we designed useful software for identification of T2DM and the healthy population to be utilized in clinical diagnosis.
Assuntos
Diabetes Mellitus Tipo 2/sangue , Aprendizado de Máquina , Obesidade/sangue , Adiponectina/análise , Biomarcadores/sangue , Glicemia/análise , Diabetes Mellitus Tipo 2/complicações , Feminino , Hemoglobinas/análise , Humanos , Insulina/análise , Nicotinamida Fosforribosiltransferase/análise , Obesidade/complicaçõesRESUMO
Drug resistance is one of the major problems, which causes recurrence of cancers. Therefore, complementary treatments are needed to improve the impacts of chemotherapy agents. The effect of probiotics as cancer-preventing agents through involvement in the activation of apoptotic pathways has been established. The present study sought to investigate how the heat-killed form of Saccharomyces cerevisiae (as a probiotic) could affect the Akt/NF-kB-induced apoptosis in colon cancer cells, the SW480 cell line. The cytotoxic effects of heat-killed yeast (HKY) and 5-fluorouracil (5-FU, as a positive control drug) were assayed using the MTT method. Morphological changes followed by apoptosis were examined using DAPI staining. The transcription and translation level of apoptosis genes were explored with qRT-PCR and western blotting. The data were analyzed using GraphPad Prism V6.0 Software. The results showed that HKY could induce apoptosis in colon cancer cell line through downregulation of p-Akt1, Rel A, Bcl-XL, pro-caspase 3, and pro-caspase 9 expressions, and upregulation of BAX, cleaved caspase-3, and cleaved caspase-9. Besides, Akt protein expression was not affected. It is noticeable that HKY had a better modulating effect on BAX expression compared with 5-FU. It was able to modulate Akt/NF-kB signaling pathway followed by the apoptotic cascade.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Probióticos/farmacologia , Saccharomyces cerevisiae , Transdução de Sinais , Antineoplásicos/administração & dosagem , Linhagem Celular Tumoral , Humanos , NF-kappa B/metabolismo , Probióticos/administração & dosagem , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
In both men and women around the world, lung cancer accounts as the principal cause of cancer-related death after breast cancer. Therefore, early detection of the disease is a cardinal step in improving prognosis and survival of patients. Today, the newly-defined microRNAs regulate about 30 to 60 percent of the gene expression. Changes in microRNA Profiles are linked to numerous health conditions, making them sophisticated biomarkers for timely, if not early, detection of cancer. Though evaluation of microRNAs in real samples has proved to be rather challenging, which is largely attributable to the unique characteristics of these molecules. Short length, sequence similarity, and low concentration stand among the factors that define microRNAs. Recently, diagnostic technologies with a focus on wide-scale point of care have recently garnered attention as great candidates for early diagnosis of cancer. Electrochemical nano-biosensors have recently garnered much attention as a molecular method, showing great potential in terms of sensitivity, specificity and reproducibility, and last but not least, adaptability to point-of-care testing. Application of nanoscale materials in electrochemical devices as promising as it is, brings multiplexing potential for conducting simultaneous evaluations on multiple cancer biomarkers. Thanks to their enthralling properties, these materials can be used to improve the efficiency of cancer diagnostics, offer more accurate predictions of prognosis, and monitor response to therapy in a more efficacious way. This article presents a concise overview of recent advances in the expeditiously evolving area of electrochemical biosensors for microRNA detection in lung cancer.
Assuntos
Biomarcadores Tumorais/isolamento & purificação , Técnicas Biossensoriais , Neoplasias Pulmonares/diagnóstico , MicroRNAs/isolamento & purificação , Biomarcadores Tumorais/genética , Técnicas Eletroquímicas , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , MicroRNAs/genética , Nanopartículas/químicaRESUMO
The present study focused on probiotic characterization and safety evaluation of Enterococcus isolates from different artisanal dairy products. All the isolates exhibited inhibitory activity against several food spoilage bacteria and food-borne pathogens, including Shigella flexneri, Staphylococcus aureus, Listeria monocytogenes, Yersinia enterocolitica, Klebsiella pneumoniae, Escherichia coli, and Bacillus subtilis. The PCR results indicated the presence of at least one enterocin structural gene in all the tested strains. The Enterococcus isolates were further evaluated regarding their safety properties and functional features. The isolates were susceptible to vancomycin, gentamycin, and chloramphenicol. The results of PCR amplification revealed that all the tested isolates harbored none of the tested virulence genes except E. faecalis (ES9), which showed the presence of esp gene. The Enterococcus isolates showed cholesterol lowering properties. The selected isolates showed a high tolerance to low pH, and toward bile salts. They also demonstrated hydrophobicity activity, auto-aggregation, and adhesion ability to the human intestinal Caco-2 cell line. These properties may contribute the bacteria colonizing the gut. This study revealed that the Enterococcus isolates, especially E. durans ES11, ES20 and ES32, might be excellent candidates for production of functional foods to promote health benefits.
RESUMO
Circulating microRNAs have been recognized as promising biomarkers for the detection of lung cancer. The objective of this study was to evaluate miR-10b, miR-1 and, miR-30a in the plasma samples of lung cancer patients to confirm any possible relevance in the early detection of lung cancer. Plasma samples from 47 non-small-cell lung cancer patients and 41 cancer-free subjects were evaluated for selected microRNAs using the real-time PCR method. To evaluate the tobacco smoking effects on microRNAs expression, the studied groups were categorized into two subgroups: never-smokers and smokers. MiR-1/miR-30a expression levels were significantly reduced in lung cancer, while the miR-10b level was significantly elevated. We found that smoking had significant effects on the levels of circulating microRNAs in the smokers of the cancer-free group (a significant up-regulation of miR-10b and significant down-regulation of miR-1/miR-30a), and lung cancer patients (a significant elevation of miR-10b). Receiver operating characteristic curve analysis showed that miR-10b with an area under the curve of 0.861, and miR-1/miR-30a with values of0.905 and 0.889 for the same parameter, could distinguish non-small-cell lung cancer patients from cancer-free subjects. Our findings demonstrated significant differences in the expression of microRNAs in lung cancer and the considerable effects of smoking on microRNAs levels. Area under curve analysis showed that miR-10b with 78% sensitivity/78% specificity, miR-1 with 95% sensitivity/80% specificity and miR-30a with 87% sensitivity/83% specificity,might be good (miR-10b/miR-30a) and excellent (miR-1) markers for lung cancer detection.