RESUMO
BACKGROUND: Multiple sclerosis (MS) is a progressive neurodegenerative disease of the central nervous system (CNS) with varying degrees of axonal and neuronal damage. The onset and progression of the disease are influenced by several environmental and genetic variables. Long non-coding RNAs (lncRNAs) have a crucial role in the pathophysiology of MS. Our study aimed to assess the levels of HAR1A and HAR1B lncRNA expression in the blood samples of MS patients and investigate the relationship between these lncRNAs and disease activity. METHODS AND RESULTS: The blood samples of 100 MS patients, including 82 relapsing-remitting (RR), 8 primary progressive (PP), and 10 secondary progressive (SP) MS cases, and 100 healthy controls were collected. Quantitative real-time PCR was used for the evaluation of gene expression. ROC curve analysis was performed to evaluate the diagnostic potential of lncRNA levels. A significant decrease was detected in HAR1A expressions (P < 0.0001), and a moderate increase was also shown in HAR1B of SPMS patients (P value = 0.0189). HAR1A showed different expression levels in patients over forty (P value = 0.034). The expression levels of HAR1A and HAR1B were positively correlated in MS patients (r = 0.2003, P value = 0.0457). In addition, ROC curve results suggested that HAR1A can be introduced as a novel biomarker for MS diagnosis (AUC = 0.776). CONCLUSION: The low serum level of HAR1A may be a potential molecular biomarker for MS diagnosis; however, no discernible difference was detected in the expression level of HAR1B in the blood samples of MS patients.
Assuntos
Esclerose Múltipla , Doenças Neurodegenerativas , RNA Longo não Codificante , Humanos , Biomarcadores , Células Sanguíneas , Estudos de Casos e Controles , Esclerose Múltipla/genética , RNA Longo não Codificante/genéticaRESUMO
BACKGROUND: The combined restoration of tumor-suppressive microRNAs (miRs) has been identified as a promising approach for inhibiting breast cancer development. This study investigated the effect of the combined restoration of miR-424-5p and miR-142-3p on MCF-7 cells and compared the efficacy of the combined therapy with the monotherapies with miR-424-5p and miR-142-3p. METHODS: After transfection of miR-424-5p and miR-142-3p mimics into MCF-7 cells in the combined and separated manner, the proliferation of tumoral cells was assessed by the MTT assay. Also, the apoptosis, autophagy, and cell cycle of the cells were analyzed by flow cytometry. Western blot and qRT-PCR were used to study the expression levels of c-Myc, Bcl-2, Bax, STAT-3, Oct-3, and Beclin-1. RESULTS: Our results have demonstrated that the combined restoration of miR-424-5p and miR-142-3p is more effective in inhibiting tumor proliferation via upregulating Bax and Beclin-1 and downregulating Bcl-2 and c-Myc. Besides, the combined therapy has arrested the cell cycle in the sub-G1 and G2 phases and has suppressed the clonogenicity via downregulating STAT-3 and Oct-3, respectively. CONCLUSION: The combined restoration of miR-424-5p and miR-142-3p is more effective in inhibiting MCF-7 breast cancer development than monotherapies with miR-424-5p and miR-142-3p.
Assuntos
Apoptose , Autofagia , Neoplasias da Mama , Ciclo Celular , MicroRNAs , Apoptose/genética , Autofagia/genética , Proteína Beclina-1/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Células MCF-7 , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
BACKGROUND: lncRNAs are modulatory factors with critical function in the tumorigenesis pathways, introducing them as promising therapeutic and diagnostic biomarkers for different cancers. This study is thus aimed to evaluate the differences in PVT1 and ZFAS1 gene expression in tumorous tissues as compared with adjacent healthy non-tumorous biopsies of gastric cancer cases. METHODS: One hundred two pairs of tumorous and adjacent non-tumorous biopsies of GC cases were sampled. RNA isolation and cDNA production were carried out. The qRT-PCR was performed to evaluate the expression of PVT1 and ZFAS1 genes. Moreover, the associations between PVT1 or ZFAS1 and clinicopathological characteristics as well as the biomarker roles of the lncRNAs were assessed. RESULTS: The PVT1 and ZFAS1 expressions showed a significant increase and decrease in GC samples as compared with non-cancerous tissues, respectively. PVT1 expression was significantly associated with and lymph-node involvement (p = 0.0007). Moreover, ZFAS1 expression demonstrated a significant association with lymph-node involvement (p = 0.0005), and tumor size >5 cm (p = 0.003). The findings of the ROC curve revealed that PVT1 and ZFAS1 may act as a possible biomarker with AUC of 0.71 and 0.79, specificity of 78.43% and 79.41%, and sensitivity of 55.88% and 64.71%. CONCLUSIONS: Regarding upregulation of PVT1 and downregulation of ZFAS1 in human GC samples, these genes may respectively act as oncogenic and tumor-suppressive factors in GC cases. Furthermore, PVT1 and ZFAS1 can be considered as possible biomarkers for the detection and treatment of GC cases.
Assuntos
Biomarcadores Tumorais/biossíntese , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/biossíntese , RNA Neoplásico/biossíntese , Neoplasias Gástricas/metabolismo , Biomarcadores Tumorais/genética , Feminino , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , RNA Longo não Codificante/genética , RNA Neoplásico/genética , Neoplasias Gástricas/genéticaRESUMO
BACKGROUND: Gastric cancer (GC) is a complicated multifactorial neoplasm with a high fatality and prevalence rate around the globe that required the discovery of many unknown mechanisms involved in its inception and progression. The aim of this project was to investigate the alterations of GClnc1 expression in cancerous tissues relative to marginal non-cancerous tissues of patients with GC and its association with clinicopathological features. METHODS: In this research, the expression level of GClnc1 was assessed using the qRT-PCR. For this, 80 pairs of cancerous and marginal non-cancerous GC samples tissues were gathered. Then RNA isolation and cDNA synthesis were carried out. Eventually, the difference of GClnc1 expression levels in tumor tissue relative to marginal non-tumor tissue specimens of GC patients and its association with pathological characteristics, as well as biomarker's performance of GClnc1, was investigated. RESULTS: Expression data examination of GClnc1 indicates increased expression in GC tumor tissues relative to marginal non-cancerous tissues (p < 0.0001). GClnc1 overexpression was significantly linked with pathological features of patients with lymph node metastasis (p = 0.037) and H. pylori infection (p = 0.029). Based on ROC analysis, the GClnc1 as a biomarker has AUC, sensitivity%, and specificity% of 0.8228, 90%, and 61.67%, respec-tively (p < 0.0001). CONCLUSIONS: Due to the GClnc1 increased expression in tumor tissues of GC patients, our research proposed that GClnc1 may be involved in the promotion and development of GC cells as a novel oncogene. Besides, in the molecular targeted therapies of GC patients, GClnc1 can be considered as a potential biomarker.
Assuntos
Infecções por Helicobacter , Helicobacter pylori , RNA Longo não Codificante , Neoplasias Gástricas , Biomarcadores Tumorais/genética , Infecções por Helicobacter/complicações , Infecções por Helicobacter/diagnóstico , Humanos , Metástase Linfática , Prognóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genéticaRESUMO
C1-inhibitor (C1INH) was shown to enhance thrombin generation (TG) in the presence of thrombomodulin (TM) by reducing production of activated protein C. Because C1INH is known to inhibit fibrinolytic system proteases, the objective of this study was to evaluate the effect of moderate (3 IU/ml) and high (16 IU/ml) C1INH concentrations on TG and plasmin generation (PG) in the presence of TM. These concentrations were evaluated based on expected maximum plasma levels following C1INH replacement therapy and recently suggested supraphysiologic dosing. TG and PG were investigated in platelet poor plasmas obtained from 21 healthy donors. An assay designed to monitor the continuous generation of the 7-amino-4-methylcoumarin fluorescence from substrates specific to thrombin or plasmin was used to evaluate the impact of C1INH activity. To characterize the C1INH effects on TG and PG, the thrombin and plasmin concentration peaks and production rates were calculated. TM addition to donor plasma shifted the concentration dependence of C1INH on TG parameters from reduction to enhancement. Conversely, PG parameters were significantly reduced by 16 IU/ml in both the presence and absence of TM. Moderate C1INH concentration (3 IU/ml) reduced TG and PG in the absence of TM but did not significantly affect these parameters in the presence of TM. Finally, 3 IU/ml of C1INH reduced PG more so than TG in the absence of TM. The presented results suggest a mechanism by which C1INH could potentiate thrombosis by inhibition of fibrinolysis.
Assuntos
Proteína Inibidora do Complemento C1/farmacologia , Fibrinolisina/antagonistas & inibidores , Trombina/efeitos dos fármacos , Trombomodulina/fisiologia , Coagulação Sanguínea , Coleta de Amostras Sanguíneas , Relação Dose-Resposta a Droga , Fibrinolisina/biossíntese , Fibrinólise/efeitos dos fármacos , Voluntários Saudáveis , Humanos , Trombina/metabolismo , Trombose/induzido quimicamenteRESUMO
OBJECTIVE: Delayed-onset muscle soreness (DOMS) often occurs after unaccustomed eccentric exercise and reduces exercise performance. We aimed to study the preventive effects of saffron and indomethacin on the biochemical and functional indicators of DOMS after 1-session eccentric exercise. DESIGN: A 10-day, randomized, double-blind, placebo-controlled, pretest-posttest design. SETTING: Controlled research laboratory. PARTICIPANTS: Thirty-nine nonactive male university students randomly divided into saffron (n = 12), indomethacin (n = 12), and control (n = 15) groups. INTERVENTIONS: Saffron group received 1 capsule containing dried saffron powder (n = 12, 300 mg/d), indomethacin group received 75 mg indomethacin (n = 12, 25 mg thrice a day), and control group (n = 15) received placebo capsules, 1 week before and 3 days after eccentric exercise. Ten days before and 24, 48, and 72 hours after muscle soreness protocol, the maximum isometric and isotonic forces, plasma creatine kinase (CK), plasma lactate dehydrogenase (LDH), perceived pain, knee range of movement, and thigh circumference were measured. Muscle soreness protocol was performed with a weight load equal to 80% of the maximum isotonic force in 4 sessions with 20 repetitions and 3-minute rest in between. MAIN OUTCOME MEASURES: This study shows that 10-day supplementation with 300 mg saffron significantly decreased the CK and LDH concentrations (P < 0.0001). In the saffron group, there was no decline in maximum isometric and isotonic forces after eccentric exercise, but a significant decline in the isometric force was observed in the control group (P < 0.0001). No pain was reported in the saffron group, whereas the indomethacin group experienced pain before 72 hours (P < 0.001). CONCLUSIONS: Results obtained from the current novel research indicate a strong preventive effect of 10-day supplementation with saffron on the DOMS. CLINICAL RELEVANCE: The saffron can be used to prevent DOMS and alleviate the DOMS symptoms.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Crocus , Indometacina/uso terapêutico , Mialgia/prevenção & controle , Fitoterapia , Treinamento Resistido , Adolescente , Creatina Quinase/metabolismo , Suplementos Nutricionais , Método Duplo-Cego , Exercício Físico , Humanos , Articulação do Joelho/fisiopatologia , L-Lactato Desidrogenase/metabolismo , Masculino , Força Muscular , Mialgia/metabolismo , Mialgia/fisiopatologia , Amplitude de Movimento Articular , Coxa da Perna , Resultado do TratamentoRESUMO
BACKGROUND: Few serological tests are available for detecting antibodies against Mycoplasma capricolum subsp. capripneumoniae, the causal agent of contagious caprine pleuropneumonia (CCPP). The complement fixation test, the test prescribed for international trade purposes, uses a crude antigen that cross-reacts with all the other mycoplasma species of the "mycoides cluster" frequently infecting goat herds. The lack of a more specific test has been a real obstacle to the evaluation of the prevalence and economic impact of CCPP worldwide. A new competitive ELISA kit for CCPP, based on a previous blocking ELISA, was formatted at CIRAD and used to evaluate the prevalence of CCPP in some regions of Kenya, Ethiopia, Mauritius, Tajikistan and Pakistan in an international collaborative study. RESULTS: The strict specificity of the test was confirmed in CCPP-free goat herds exposed to other mycoplasma species of the "mycoides cluster". Prevalence studies were performed across the enzootic range of the disease in Africa and Asia. Seroprevalence was estimated at 14.6% in the Afar region of Ethiopia, whereas all the herds presented for CCPP vaccination in Kenya tested positive (individual seroprevalence varied from 6 to 90% within each herd). In Mauritius, where CCPP emerged in 2009, nine of 62 herds tested positive. In Central Asia, where the disease was confirmed only recently, no positive animals were detected in the Wakhan District of Afghanistan or across the border in neighboring areas of Tajikistan, whereas seroprevalence varied between 2.7% and 44.2% in the other districts investigated and in northern Pakistan. The test was also used to monitor seroconversion in vaccinated animals. CONCLUSIONS: This newly formatted CCPP cELISA kit has retained the high specificity of the original kit. It can therefore be used to evaluate the prevalence of CCPP in countries or regions without vaccination programs. It could also be used to monitor the efficacy of vaccination campaigns as high-quality vaccines induce high rates of seroconversion.
Assuntos
Ensaio de Imunoadsorção Enzimática/veterinária , Doenças das Cabras/epidemiologia , Mycoplasma capricolum , Pleuropneumonia Contagiosa/microbiologia , Pleuropneumonia/veterinária , Animais , Anticorpos Monoclonais , Vacinas Bacterianas/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Saúde Global , Doenças das Cabras/microbiologia , Cabras , Internacionalidade , Pleuropneumonia/epidemiologia , Pleuropneumonia Contagiosa/epidemiologia , Pleuropneumonia Contagiosa/prevenção & controle , Estudos SoroepidemiológicosRESUMO
BACKGROUND: Platelet storage is complicated by deleterious changes, among which reduction of ristocetin-induced platelet aggregation (RIPA) has a poorly understood mechanism. The study elucidates the mechanistic roles of all the possible players in this process. RESEARCH DESIGN AND METHODS: PRP-platelet concentrates were subjected to RIPA, collagen-induced platelet aggregation (CIPA), and flowcytometric analysis of GPIbα and PAC-1 binding from days 0 to 5 of storage. Platelet-poor plasma was subjected to colorimetric assays for glucose/LDH evaluation and automatic analyzer to examine VWF antigen and activity. RESULTS: From day three of platelet storage, reducing CIPA but not RIPA was correlated with the reduction of both metabolic state and integrin activity. RIPA reduction was directly related to the decreased levels of total-content/expression of GPIbα, and inversely related to its shedding levels during storage. Re-suspension of 5-day stored platelet in fresh plasma compensated CIPA, but not RIPA. VWF concentration and its activity did not change during storage while they had no correlation with RIPA. CONCLUSIONS: This study identified the irreversible loss of platelet GPIbα, but not VWF status, as the primary cause of the storage-dependent decrease of RIPA. Unlike CIPA, this observation was not compensated by plasma refreshment, suggesting that some evidence of PSL may not be recovered after transfusion.
Assuntos
Plaquetas , Preservação de Sangue , Agregação Plaquetária , Complexo Glicoproteico GPIb-IX de Plaquetas , Ristocetina , Fator de von Willebrand , Humanos , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Agregação Plaquetária/efeitos dos fármacos , Ristocetina/farmacologia , Plaquetas/metabolismo , Preservação de Sangue/métodos , Fator de von Willebrand/metabolismo , Hemostasia/efeitos dos fármacosRESUMO
Breast cancer (BC) is the second most common malignancy worldwide. ADGRL4, as a modulator of angiogenesis, undergoes various epigenetic modifications affecting its biological functions. In this study, we aimed to assess ADGRL4 promoter methylation status and its expression levels in primary breast tumors and to evaluate its potency as a plausible prognostic biomarker in BC. Furthermore, we evaluated the effect of melatonin on ADGRL4 expression and viability of BC cells in vitro. One hundred breast tumor tissue samples and adjacent non-tumor tissues were collected, followed by DNA isolation, bisulfite conversion, qRT-PCR, qMSP assay, and immunoblotting. In addition, four BC cell lines were treated with melatonin and subjected to ADGRL4 expression analysis and apoptosis assay. We found a significant correlation between ADGRL4 expression levels and HER2 status and stage of disease (P < 0.05). We observed a substantial attenuation in ADGRL4 promoter methylation in tumor samples compared to marginal non-tumor samples. A significantly lower expression of ADGRL4 was detected in two BC cell lines in the presence of melatonin. MCF-7 and BT474 melatonin-treated cell lines showed a significantly higher number of apoptotic cells than non-treated cells (P < 0.0001). Based on the receiver operating characteristic (ROC) curve analysis, ADGRL4 expression and ADGRL4 promoter methylation status showed moderate prognostic value. We found that melatonin has anti-cancer effects on BC cells. In addition, ADGRL4 expression can potentially be used as a prognostic biomarker in BC.
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BACKGROUND: MS (Multiple sclerosis) is a progressive neurologic disorder often appearing in the third decade of life. MS is the most frequent demyelinating disease of the central nervous system. The development of MS is influenced by environmental, genetic, and epigenetic factors. The bulk of the human transcriptome comprises lncRNAs, which play crucial regulatory roles. We aimed to assess the SNHG3 and BCYRN1 lncRNA expression in blood samples from MS patients and how these lncRNAs and disease activity are related. METHODS: A total of 100 MS patients, including 8 primary progressive (PP), 82 relapsing-remitting (RR), and 10 secondary progressive (SP) MS, as well as 100 healthy controls, had their blood samples taken. Gene expression was assessed using quantitative real-time PCR. Recognizing the receiver operating characteristic (ROC) curve analysis, the diagnostic potential of lncRNA levels was evaluated. RESULTS: Expressions of SNHG3 and BCYRN1 were found to have significantly increased (p < 0.0001). SNHG3 expression level showed significant differences compared to age groups and MS subtypes (p value = 0.001 and p value = 0.02).Furthermore, patients with a family history showed elevated BCYRN1 expression with a p value of 0.01. Considering the age factor, BCYRN1 exhibits altered expression levels in patient groups compared to healthy controls (p value 0.04). Additionally, the novel biomarkers SNHG3 and BCYRN1 can be used to diagnose MS (AUC = 0.97 and AUC = 0.88, respectively). DISCUSSION: Increased levels of SNHG3 and BCYRN1 in the serum may serve as potential molecular biomarkers for the MS diagnosis.
Assuntos
Esclerose Múltipla , RNA Longo não Codificante , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Biomarcadores/sangue , Esclerose Múltipla/sangue , Esclerose Múltipla/genética , Esclerose Múltipla/diagnóstico , RNA Longo não Codificante/sangue , RNA Longo não Codificante/genética , Curva ROCRESUMO
Background: Long noncoding RNAs (lncRNAs) as critical molecules play an essential role in the development of cancers. In colorectal cancer (CRC), various lncRNAs are related to cell proliferation, apoptosis, migration, and invasion. LncRNA prostate cancer-associated transcript 1 (PCAT-1), as an oncogenic factor, is a diagnostic biomarker that regulates cell proliferation, migration, invasion, and apoptosis. Methods: This study evaluated the relationship between PCAT-1, CRC occurrence, and pathological features of Iranian patients. The studied samples included 100 colorectal tumor tissues and 100 adjacent healthy tissues of Iranian CRC patients. RNAs were extracted from cancerous and noncancerous tissues to synthesize complementary DNA. The expression level of PCAT-1 was assessed using the real-time PCR method, and the data analysis was assessed using SPSS software. Results: In this study, expression level of PCAT-1 in tumor tissue was significantly increased in Iranian patients, and pathological studies of the patients had no significant relationship with the PCAT-1 expression profile. Conclusion: Our results suggested that the high expression of PCAT-1 resulted in the occurrence of colorectal tumor tissues in Iranian patients, which can be considered a diagnostic biomarker in CRC.
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Neoplasias Colorretais , RNA Longo não Codificante , Humanos , Masculino , Apoptose/genética , Biomarcadores , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Irã (Geográfico) , RNA Longo não Codificante/metabolismo , Regulação para Cima/genéticaRESUMO
This study was conducted to investigate the effects of 12 weeks of aerobic exercise (AT) and saffron supplementation on hemostasis, inflammatory markers, and insulin resistance in obese women diagnosed with type 2 diabetes (T2D). A total of 44 women with T2D (mean age: 54.12 ± 5.63 years, mean BMI: 31.15 ± 1.50 kg/m2, HbA1c: 85 ± 4.2 mmol/mol) were included in a randomized, double-blind, placebo-controlled study. We were randomly assigned to one of four groups (n = 11 per group): saffron + training (ST), placebo + training (PT), saffron supplement (SS), and placebo (P). The ST and PT groups completed 12 weeks of AT (three sessions per week of mild to moderate intensity). The ST and SS groups were administered a daily dose of 200 mg of saffron powder for 12 weeks. Fasting blood samples were collected 48 h before the first AT session and/or nutritional supplementation and 48 h after the last AT session and/or nutritional supplementation. Post-evaluation, homeostatic model assessment of insulin resistance value (HOMA-IR, p < 0.001) and serum levels of glucose (p < 0.001), fibrinogen (FIB, p < 0.001), homocysteine (HCY, p < 0.001), interleukin-6 (IL-6, p < 0.001), and tumor necrosis factor α (TNFα, p < 0.001) showed significant reduction in the ST, PT, and SS groups compared to the P group (p < 0.05). In particular, the ST group showed a more significant reduction in all variables compared to the PT and SS groups (p < 0.05). Our results suggest that a 12-week intervention with AT and saffron supplementation can independently improve markers related to hemostasis, inflammation, and insulin resistance. However, their combination showed the greatest effectiveness on the above markers.
Assuntos
Biomarcadores , Crocus , Diabetes Mellitus Tipo 2 , Suplementos Nutricionais , Exercício Físico , Resistência à Insulina , Humanos , Feminino , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/sangue , Método Duplo-Cego , Pessoa de Meia-Idade , Biomarcadores/sangue , Exercício Físico/fisiologia , Inflamação/sangue , Interleucina-6/sangue , Obesidade/terapia , Obesidade/sangue , Glicemia/análise , Fator de Necrose Tumoral alfa/sangue , HemostasiaRESUMO
Aim: MicroRNAs can be regarded as biomarkers for gastric cancer (GC) diagnosis in the early stages. This study assesses the expression levels of miR-362-3p, miR-362-5p and miR-363-5p as potential biomarkers for GC.Materials & methods: The expression levels of the miRNAs in 90 pairs of GC and adjacent normal tissue samples were analyzed by quantitative real-time reverse transcription PCR (qRT-PCR) and some bioinformatics tools were utilized for analyzing the target genes and possible molecular pathways in which these miRNAs participate.Results & conclusion: There was a significant overexpression of the miRNAs in GC cells and an outstanding correlation between their overexpression with some clinicopathological features of the patients.
[Box: see text].
Assuntos
Biomarcadores Tumorais , MicroRNAs , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/metabolismo , MicroRNAs/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Feminino , Masculino , Pessoa de Meia-Idade , Regulação Neoplásica da Expressão Gênica , Idoso , AdultoRESUMO
Zymosan is a ß-glucan isolated from Saccharomyces cerevisiae that could be employed for drug delivery. We synthesized zymosan nanoparticles and measured their structural and morphological properties using XRD, UV-Vis spectroscopy, TEM and AFM. The loading of doxorubicin (DOX) onto the nanoparticles was confirmed by FT-IR, and the DOX release was shown to be pH-dependent. The effect of these agents on C26 cell viability was evaluated by MTT tests and the expression of genes connected with the Wnt/ß-catenin pathway and apoptosis were analyzed by RT-qPCR and Western blotting. Treatments were able to suppress the proliferation of C26 cells, and the zymosan nanocarriers loaded with DOX enhanced the anti-proliferative effect of DOX in a synergistic manner. Zymosan nanoparticles were able to suppress the expression of cyclin D1, VEGF, ZEB1, and Twist mRNAs. Treatment groups upregulated the expression of caspase-8, while reducing the Bax/Bcl-2 ratio, thus promoting apoptosis. In conclusion, zymosan nanoparticles as DOX nanocarriers could provide a more targeted drug delivery through pH-responsiveness, and showed synergistic cytotoxicity by modifying Wnt/ß-catenin signaling and apoptosis.
Assuntos
Neoplasias Colorretais , Nanopartículas , Humanos , Doxorrubicina/química , beta Catenina/metabolismo , Zimosan , Via de Sinalização Wnt , Espectroscopia de Infravermelho com Transformada de Fourier , Apoptose , Nanopartículas/química , Neoplasias Colorretais/tratamento farmacológicoRESUMO
Border fences have severely impeded the transboundary migration of a number of large mammals worldwide, with central Asia being one of the most impacted. The Marco Polo sheep (Ovis ammon polii), an iconic species of Pamir, is threatened in its transboundary movement by increasing border fencing among their five distributed countries, including Tajikistan, Kyrgyzstan, China, Afghanistan, and Pakistan. In this study, by building ensemble species distribution models, we found that eastern Tajikistan had the largest suitable Macro Polo sheep habitat (about 42 % of the total suitable habitat), followed by China (about 32 %). We used least-cost paths to identify 51 ecological corridors including 5 transboundary ecological corridors, which may be important to maintain connectivity in both domestic and transboundary regions. To assess the potential barrier effect of border fences, we assessed four scenarios (30, 40, 50 and 60°) corresponding to the upper limit of the slope for the construction of fences. In areas too steep for fencing, these could be used by wild sheep to cross barriers or borders and may represent migration or movement routes, defined as natural passages. In the most pessimistic Scenario 60, only 25 migratory passages along the border fences were identified, compared to 997 in the most optimistic scenario (Scenario 30), indicating a strong negative effect of intensive border fencing on the transboundary movement of Marco Polo sheep. The establishment of transnational conservation parks, and ensuring permeability is maintained in key areas, could have a positive impact on the connectivity and persistence of Marco Polo sheep populations, and provide important lessons for other large migratory mammals in transboundary regions.
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Ecossistema , Mamíferos , Animais , Ovinos , China , Afeganistão , Quirguistão , Conservação dos Recursos NaturaisRESUMO
BACKGROUND: Gastric cancer is the fifth most frequent cancer worldwide and the fourth leading cause of death from cancer, a complex multifactorial neoplasm. LncRNAs are regulatory RNA molecules larger than 200 nucleotides, which can have profound effects on the oncogenic process of various types of cancer. Therefore, these molecules can be used as diagnostic and therapeutic biomarkers. This study aimed to determine the differences in BOK-AS1, FAM215A, and FEZF1-AS1 gene expression between tumor tissue and adjacent healthy non-tumor tissue of gastric cancer (GC) patients. METHODS: In this study one hundred pairs of cancerous and non-cancerous marginal tissues were gathered. Next, RNA extraction and cDNA synthesis were achieved for all of the samples. Then, the qRT-PCR was performed to measure the expression of BOK-AS1, FAM215A and FEZF1-AS1 genes. RESULTS: All BOK-AS1, FAM215A and FEZF1-AS1 genes showed significantly increased expression in tumor tissues compared with non-tumor tissues. The outcome of the ROC analysis demonstrated that BOK-AS1, FAM215A, and FEZF1-AS1 may act as mean biomarkers with AUC of 0.7368, 0.7163 and 0.7115, specificity of 64%, 61% and 59%, and sensitivity of 74%, 70%, and 74% respectively. CONCLUSION: Based on the increased expression of the BOK-AS1, FAM215A and FEZF1-AS1 genes in GC patients, this study suggests that these genes may function as oncogenic factors. Furthermore, the mentioned genes can be considered as intermediate biomarkers for diagnosis and treatment of gastric cancer. In addition, no association between these genes and clinicopathological features was observed.
Assuntos
RNA Longo não Codificante , Neoplasias Gástricas , Humanos , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Repressoras/genética , RNA Longo não Codificante/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Regulação para CimaRESUMO
Objectives: One of the most common methods used for the reconstruction of endodontically treated teeth is post and core and crown. Various factors such as the remaining tissue above the cutting margin (ferrule) affect the fracture resistance of teeth restored with post and core and crown. This study aimed to investigate the effect of ferrule/crown ratio (FCR) on the strength of maxillary anterior central teeth using finite element analysis. Materials and Methods: A 3D scan of a central incisor was obtained, and the data were transferred to Mimics software. Then, a 3D model of the tooth was designed. Next, 300N load was applied at a 135° angle to the tooth model. Force was applied to the model both horizontally and vertically. Ferrule height was considered to be 5%, 10%, 15%, 20%, and 25% in the palatal surface and 50% in the buccal surface. The length of post in the model was 11, 13, and 15mm. Results: By increasing the FCR, stress and strain distribution increased in the dental model and decreased in the post itself. As the horizontal angle of load application increased, the level of stress and strain created in the dental model increased as well. The closer the force application site to the incisal area, the higher the stress and strain would be. Conclusion: Maximum stress was inversely correlated with FCR and post length. In ratios of 20% and higher, insignificant changes occurred in stress and strain patterns in the dental model.
RESUMO
PURPOSE: Gastric cancer (GC) has been identified worldwide as one of the most common cancer types with a high mortality rate. LncRNA SDMGC has been recognized as an oncogene with regulatory effects on its target gene, TRIM16, which is believed to play a tumor-suppressing role in various cancers. Both these genes are involved in GC development, tumorigenesis, invasion, and metastasis. The current study is aimed to investigate the association of SDMGC and TRIM16 with GC susceptibility and GC patients' clinicopathological characteristics. METHODS: A total of 100 GC tissues and their corresponding adjacent non-tumor tissues were sampled. Total RNA was then isolated to measure SDMGC and TRIM16 expression levels using quantitative reverse transcriptase (qRT)-PCR. Statistical analyses including the Mann-Whitney U test and correlation tests were carried out using R v4.5. GraphPad Prism was also used to plot the receiver operating curve (ROC). RESULTS: The results demonstrated the significant overexpression of lncRNAs SDMGC and downregulation of TRIM16 in GC tissues as compared to their corresponding marginal normal tissue samples (P = 0.005 and P = 0.009, respectively). No association with clinicopathological variables was observed for either SDMGC or TRIM16. Moreover, the results demonstrated a small positive correlation between SDMGC and TRIM16. Evaluation of the diagnostic value of SDMGC and TRIM16 showed poor biomarker potency for these genes. CONCLUSION: In conclusion, the results indicated an increase in the expression of SDMGC and a decline in the expression pattern of TRIM16 among the Iranian population. The results indicated a key tumor-accelerative function of SDMGC and a pivotal tumor-suppressing role of TRIM16 in GC patients.
Assuntos
RNA Longo não Codificante , Neoplasias Gástricas , Humanos , RNA Longo não Codificante/metabolismo , Prognóstico , Neoplasias Gástricas/patologia , Irã (Geográfico) , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Proteínas com Motivo Tripartido/genética , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismoRESUMO
lncRNAs play a crucial role in the carcinogenesis process. Thus, they have been recognized as the potential therapeutic and diagnostic biomarkers of cancers. This study assessed the alteration in the expression of APOC1P1-3 lncRNA in cancerous tissues compared to their adjacent non-tumorous tissues sampled from cervical cancer patients. one hundred fifteen pairs of cancerous and adjacent non-cancerous biopsy of cervical cancer specimens were collected. RNA isolation and cDNA synthesis were carried out. The qRT-PCR was used to assess the changes in the expression of APOC1P1-3 lncRNA. Moreover, the biomarker function of the lncRNA and the correlations between APOC1P1-3 and clinicopathological parameters were measured. The APOC1P1-3 expression was significantly increased in cervical cancer specimens as compared to adjacent non-tumorous specimens (p < 0.0001). A significant association was also observed between APOC1P1-3 expression and lymph node involvement (p = 0.031). Additionally, APOC1P1-3 expression demonstrated a significant association with the depth of tumor invasion (p = 0.035), and squamous type of cervical cancer (p = 0.019). The overexpression of APOC1P1-3 was significantly observed in patients younger than 50 years old as compared to another age group (p = 0.033). The results of ROC curve exhibited that APOC1P1-3 with area under the curve (AUC), specificity, and sensitivity of 0.96, 93.91%, and 78.26%, respectively can be considered as a potential biomarker. Regarding overexpression of APOC1P1-3 in human cervical cancer samples, this lncRNA may be considered as an oncogenic factor in cervical cancer patients. Besides, APOC1P1-3 may be a possible biomarker for the diagnosis and treatment of cervical cancer patients.
Assuntos
RNA Longo não Codificante , Neoplasias do Colo do Útero , Feminino , Humanos , Pessoa de Meia-Idade , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão GênicaRESUMO
Background: A critical role has been known for lncRNAs in the initiation and development of cancers. Therefore, lncRNAs have been reported as the possible biomarkers in relation to the diagnosis and therapy of malignancies. This project examined the change in CYTOR lncRNA expression in human cervical cancer samples as compared with adjacent healthy ones. Methods: We provided one hundred fifteen pairs of tumorous and adjacent healthy tissue specimens of cervical cancer patients. RNAs were isolated from tissue specimens and cDNAs were synthesized. We considered quantitative Real-time PCR (qRT-PCR) to examine the expression levels of CYTOR lncRNA. In addition, the biomarker activity of CYTOR and the associations between the lncRNA and clinicopathological characteristics were evaluated. Results: The significant increased expression of CYTOR was obtained in cancerous samples as compared with non-cancerous ones (P< 0.0001). A significant correlation was indicated between CYTOR expression and the squamous subtype of cervical cancer (p=0.046). The receiver operating characteristic (ROC) curve-related AUC (area under the curve), specificity, and sensitivity were calculated 0.88, 81.74%, and 80%, respectively, which may introduce CYTOR as a potential biomarker. Conclusion: CYTOR may be an effective oncogene and biomarker in cervical cancer cases given its increased expression in human cervical cancer tissues.