RESUMO
BACKGROUND: Multiple sclerosis (MS) is a complex autoimmune disease that affects the central nervous system, causing inflammation, demyelination, and neurodegeneration. Understanding the dysregulation of Tregs, dynamic cells involved in autoimmunity, is crucial in comprehending diseases like MS. However, the role of lymphocyte-activation gene 3 (Lag-3) in MS remains unclear. METHODS: In this study, we explore the potential of exosomes derived from human umbilical cord mesenchymal stem cells (hUMSCs-Exs) as an immune modulator in experimental autoimmune encephalomyelitis (EAE), a model for MS. RESULTS: Using flow cytometry, our research findings indicate that groups receiving treatment with hUMSC-Exs revealed a significant increase in Lag-3 expression on Foxp3 + CD4 + T cells. Furthermore, cell proliferation conducted on spleen tissue samples from EAE mice using the CFSE method exposed to hUMSC-Exs yielded relevant results. CONCLUSIONS: These results suggest that hUMSCs-Exs could be a promising anti-inflammatory agent to regulate T-cell responses in EAE and other autoimmune diseases. However, further research is necessary to fully understand the underlying mechanisms and Lag-3's precise role in these conditions.
Assuntos
Encefalomielite Autoimune Experimental , Exossomos , Células-Tronco Mesenquimais , Esclerose Múltipla , Animais , Humanos , Camundongos , Células-Tronco Mesenquimais/metabolismo , Cordão UmbilicalRESUMO
Purpose: Despite the high prevalence of gastric cancer (GC), drug resistance is a major problem for effective chemotherapy. B7-H7 is a novel member of the B7 superfamily and is expressed in most common cancers. However, the role of B7-H7 on the aggressiveness of GC and chemosensitivity has remained unknown. Therefore, this study was designed to assess the effect of B7-H7 suppression using small interference RNA (siRNA) in combination with docetaxel on GC cells. Methods: MTT test was applied to determine the IC50 of docetaxel and the combined effect of B7-H7 siRNA and docetaxel on the viability of the MKN-45 cells. To determine B7-H7, BCL-2, BAX, and caspase-3-8-9 genes expression, qRT-PCR was performed. Furthermore, flow cytometry was applied to evaluate apoptosis and the cell cycle status. Finally, to evaluate the effect of this combination therapy on migratory capacity and colony-forming ability, wound healing assay and colony formation test were employed, respectively. Results: B7-H7 suppression increased the chemo-sensitivity of MKN-45 cells to docetaxel. The expression of B7-H7 mRNA was reduced after using B7-H7 siRNA and docetaxel in MKN-45 GC cells. Also, B7-H7 suppression alongside docetaxel reduced cell migration and colony formation rate, arrested the cell cycle at the G2-M phase, and induced apoptosis by modulating the expression of apoptotic target genes. Conclusion: B7-H7 plays a significant role in the chemo-sensitivity and pathogenesis of GC. Therefore, B7-H7 suppression, in combination with docetaxel, may be a promising therapeutic approach in treating GC.
RESUMO
PURPOSE: The purpose of this study was to investigate the long-term clinical outcome of keratolimbal allograft (KLAL) alone or in combination with keratoplasty, in the management of patients with chronic and delayed-onset mustard gas keratopathy (MGK). METHODS: Patients who had KLAL for MGK with or without corneal transplantation between 2002 and 2016 were recalled to be enrolled in this retrospective interventional case series. The primary outcome was the success rate of the KLAL demonstrated by Kaplan-Meier cumulative survival analysis. The secondary outcomes were postoperative BCVA and the need for further surgery. RESULTS: A total of 108 eyes of 68 patients with MGK underwent KLAL. All patients were male with an average age of 54 ± 6 years with an average follow-up duration of 81.9 ± 38.4 months. Sectoral KLAL alone was performed in 62 eyes (57.4%), combined with lamellar keratoplasty (LKP) in 40 eyes (37%) and combined with penetrating keratoplasty in 6 eyes (5.6%). The cumulative probability of success was 75% within the follow-up duration. The mean duration of successful KLAL survival was 80.6 ± 38 months. 88.1% of these eyes needed only 1 operation to stabilize the ocular surface. Average BCVA did not improve significantly after KLAL alone, except in those accompanied by keratoplasty. KLAL combined with LKP achieved the superior clinical outcome compared with KLAL alone. Infectious keratitis occurred in 6 eyes (5.5%). No adverse event due to postoperative systemic immunosuppression was observed. CONCLUSIONS: KLAL alone or combined with LKP is effective, durable, and visually acceptable in the reconstruction of ocular surface in patients with limbal stem cell deficiency secondary to MGK.
Assuntos
Doenças da Córnea , Transplante de Córnea , Limbo da Córnea , Gás de Mostarda , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Transplante de Células-Tronco , Limbo da Córnea/cirurgia , Doenças da Córnea/cirurgia , Ceratoplastia Penetrante , AloenxertosRESUMO
OBJECTIVE: Multiple myeloma (MM) is known as an incurable heterogeneous plasma cell malignancy that presents with a variety of clinical manifestations. Inflammation plays an important role in this disease. Cytokines and Chemokines cause the progression of the disease. One of them is interleukin-1ß (IL-1ß), which may be involved in the pathogenesis of MM. Other markers such as calcium, albumin, creatinine, globulins, and total protein are also used to diagnose and prognosis patients. The main purpose of this study was to evaluate the serum level of IL-1ß and various forms of calcium (total calcium, ionized calcium, and corrected calcium), albumin, creatinine, globulin, and total protein on stage-I of MM patients and healthy controls. METHODS: Serum samples from 30 stage-I MM patients and 30 healthy subjects as controls were examined in this study. The protein concentrations of serum IL-1ß was assessed by enzyme-linked immunosorbent assay (ELISA), total calcium, albumin, creatinine, total protein, and globulin Measured by auto analyzer BT3000, an electrolyte analyzer was used to measure ionized calcium (Ca++) and a special equation was used to calculate the corrected calcium. RESULT: The mean level of IL-1ß was significantly elevated in stage-I MM. The mean levels of IL-1ß were 7.04±1.15 ng/ml in stage-I MM and 3.12± 0.90 ng/ml in controls (p<0.001). The mean levels of total calcium (total Ca) were 9.45±0.56 mg/dl in stage-I MM and 9.09±0.43mg/dl in controls (p=0.008). The mean levels of ionized calcium (Ca++) was 4.65±0.28mg/dl in stage-I MM and 4.75±0.33mg/dl in controls (p=0.2). The mean ratio of serum ionized calcium to total calcium (Ca++/ total Ca) was 0.49±0.054 in stage-I MM and 0.52±0.047 in controls (p=0.02). The mean ratio of serum ionized calcium to corrected calcium (Ca++/corrected Ca) was 0.42±0.033 in stage-I MM and the Mean ratio of serum ionized calcium to calcium total (Ca++/ total Ca) was 0.52±0.047 in controls, Comparison of the mean of the two groups shows a significant difference (p<0.001). The mean level of albumin was 1.72±0.35 g/dl in stage-I MM and4.32±0.41g/dl in controls (p<0.001). The mean level of total protein was 12.65±0.81g/dl in stage-I MM and 7.07±0.4 g/dl in controls (p<0.001). The mean level of globulin was 11.00±0.96 mg/dl in stage-I MM and 2.85±0.77 mg/dl in controls (p<0.001). The mean level of creatinine was 1.15±0.25 mg/dl in stage-I MM and 0.96±0.15 mg/dl in controls (p=0.001). CONCLUSION: The results of the study indicate the possible involvement of IL-1ß at stage-I MM and it can indicate the role of chemokines in the disease process, especially in the early stages. Changes in the chemical profiles mentioned can help in the diagnosis and prognosis of the disease.
Assuntos
Mieloma Múltiplo , Albuminas , Cálcio , Quimiocinas , Creatinina , Citocinas , Progressão da Doença , Humanos , Interleucina-1beta , Mieloma Múltiplo/patologiaRESUMO
BACKGROUND: Histone deacetylase 3 (HDAC3) is a potential oncogene that is significantly up-regulated in patients with breast cancer. MicroRNAs (miRs) are a group of small non-coding and regulatory RNAs which have recently been proposed as promising molecules for breast cancer target therapy. In the current study, we investigated the impact of miR-589-5p/ HDAC3 axis on cancer cell development in triple negative breast cancer (TNBC) cells. METHODS: In-silico analysis determined that miR-589-5p potentially targets HDAC3. We evaluated the HDAC3 and mir-589-5p expression levels in clinical samples and breast cancer cell lines including MDA-MB-231, MDA-MB-468, MCF-7 and MCF-10A. HDAC3 was knocked out to investigate its role on cancer cell progression. Anti-cancerous role of the miR-589-5p was assessed using an expression vector. We evaluated possible alteration in the cell cycle progression, cell viability and cell proliferation, after transient transfection. RESULTS: HDAC3 was over-expressed in TNBC clinical samples and breast cancer cell lines compared to non-cancerous controls while miR-589-5p was down regulated in cancer cells. Suppression of HDAC3 decreased the cell viability, cell proliferation and colony formation. Similar results were observed after over-expression of the miR-589-5p. Dual-Luciferase reporter assay confirmed the direct targeting of HDAC3 by miR-589-5p. CONCLUSION: Our results showed that miR-589-5p mediates its anti-proliferative effects on breast cancer cells via targeting HDAC3. These findings suggest that the miR-589-5p/ HDAC3 axis could be considered as a possible therapeutic strategy in TNBC.
Assuntos
Neoplasias da Mama , MicroRNAs , Neoplasias de Mama Triplo Negativas , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Histona Desacetilases , Humanos , MicroRNAs/genética , Invasividade Neoplásica/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismoRESUMO
It has been recently revealed that Histone Deacetylase (HDAC) 3, a unique member of the HDACs family, can trigger and progress cancers by alternation in genes expression and proteins activity. Epigenetic modifications by HDACs have been studied well in various cancer cells. Recent studies have focused on the HDAC enzymes as a possible target in cancer therapy. There are significant documents on upregulation of HDAC3 in breast cancer (BC) cells which suggest an oncogenic role for this enzyme. Interestingly, some studies showed that HDAC3 inhibition could be considered as a promising target in breast cancer therapy, and thus far, several inhibitors from different nature have been introduced. In this review, we discussed the function and highlight the existing inhibitors of HDAC3 in BC pathogenesis and therapy.
Assuntos
Neoplasias da Mama , Inibidores de Histona Desacetilases , Histona Desacetilases , Neoplasias da Mama/patologia , Epigênese Genética , Feminino , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , HumanosRESUMO
PURPOSE: Anti-cancer and anti-migration effects of lupeol as a biological pentacyclic triterpenoid were investigated individually and in combination with Doxorubicin (DOX) on MCF-7 and MDA-MB-231 breast cancer cells and human foreskin fibroblasts. METHODS: To uncover the anticancer effect of lupeol and the impact of its combination with DOX, cell viability and scratch assays and dual acridine-orange apoptotic staining were performed. Moreover, the expression of proapoptotic caspase-3 and metastasis-related MMP-9 at the mRNA and protein levels was analyzed using qPCR and western blot techniques. RESULTS: Lupeol synergistically increased the anti-proliferative effect of DOX with IC50 values of 42.55, 62.24 and 65.9 µM on MCF-7, MDA-MB-231 and HFF cells, respectively. Lupeol reduced the cell migration and lowered the DOX-induced cell migration, significantly (p < 0.05). The number of apoptotic cells elevated significantly (p < 0.05) when cancer cells were treated with the combination of lupeol and DOX. Lupeol individually and in combination with DOX up-regulated the expression of caspase-3. The proposed combination therapy synergized (3-4 fold) the down-regulation of MMP-9 expression in MCF-7 and MDA-MB-231 cells. CONCLUSION: Our results indicate that lupeol could be considered as an anticancer agent and anticancer adjuvant in breast cancer-therapy. The anticancer properties of lupeol attribute to its antiproliferative, antimigrative and apoptotic effects.
Assuntos
Neoplasias da Mama , Apoptose , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Caspase 3/genética , Linhagem Celular Tumoral , Proliferação de Células , Doxorrubicina/farmacologia , Feminino , Humanos , Células MCF-7 , Metaloproteinase 9 da Matriz/genética , Triterpenos PentacíclicosRESUMO
Coronavirus disease 2019 or COVID-19, starting from Wuhan, China, in December 2019, is a pandemic situation affecting millions worldwide and has exerted a huge burden on healthcare infrastructure. Therefore, there is an urgent need to understand the molecular mechanisms underlying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and design novel effective therapeutic strategies for combating this pandemic. In this regard, special attention has been paid to the exosomes. These nanoparticles are extracellular vesicles with critical function in the pathogenesis of several diseases including viral sepsis. Therefore, they may be involved in the pathogenesis of COVID-19 infection and also may be a way for transferring viral components and infecting other neighbor cells. Exosomes also can be considered as a therapeutic strategy for treating COVID-19 patients or used as a carrier for delivering effective therapeutic agents. Therefore, in this review, we discussed the biogenesis and contents of exosomes, their function in viral infection, and their potential as a therapeutic candidate in treating COVID-19.
RESUMO
BACKGROUND: The present study was conducted to investigate the therapeutic effects of a potent polyphenol, fisetin, on the letrozole-induced rat model of polycystic ovary syndrome (PCOS). METHODOLOGY: Twenty-four female Wistar rats (42 days old) were divided into four groups: control group (received carboxy methylcellulose (CMC 0.5 %)), PCOS group treated with letrozole (1 mg/kg), fisetin group received same dose of letrozole + fisetin (10 mg/kg), and metformin group received same dose of letrozole + metformin (300 mg/kg). At the end of the experiment, biochemical (glucose, lipid profile) and hormonal (insulin, testosterone, estradiol, and progesterone) parameters were analyzed. Histological examinations of ovaries were also conducted by hematoxylin and eosin (H&E) staining. Real-time polymerase chain reaction (PCR) and western blotting were carried out for cytochrome P450 17A1 (CYP17A1), sirtuin-1 (SIRT1), and 5' AMP-activated protein kinase (AMPK) gene expression in the ovaries. Furthermore, enzymatic activities of antioxidants including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the ovaries were analyzed by colorimetric method. RESULTS: Letrozole administration resulted in a remarkable abnormality in biochemical and hormonal parameters. Fisetin normalized levels of glucose, lipid profile, homeostatic model assessment for insulin resistance (HOMA-IR), testosterone, estradiol, and progesterone. Moreover, fisetin increased expression levels of SIRT1 and AMPK, and decreased expression level of CYP17A1 in the ovaries. Additionally, fisetin showed protective effect by enhancing antioxidant activities of CAT, SOD, and GPx depleted secondary to induction of PCOS. Fisetin effects were comparable to metformin, as the standard drug used for treatment of PCOS. CONCLUSION: Our results showed that, fisetin treatment caused significant alleviating effects by restoring PCOS-induced alterations in the key genes involved in energy homeostasis and antioxidant enzymes, suggesting that it may have a key role in combating with PCOS.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Flavonóis/farmacologia , Letrozol/antagonistas & inibidores , Ovário/efeitos dos fármacos , Síndrome do Ovário Policístico/tratamento farmacológico , Proteínas Quinases Ativadas por AMP/sangue , Proteínas Quinases Ativadas por AMP/genética , Animais , Glicemia/metabolismo , Carboximetilcelulose Sódica/administração & dosagem , Catalase/sangue , Catalase/genética , Modelos Animais de Doenças , Estradiol/sangue , Feminino , Expressão Gênica , Glutationa Peroxidase/sangue , Glutationa Peroxidase/genética , Humanos , Insulina/sangue , Letrozol/toxicidade , Metformina/farmacologia , Ovário/metabolismo , Ovário/patologia , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/patologia , Progesterona/sangue , Ratos , Ratos Wistar , Sirtuína 1/sangue , Sirtuína 1/genética , Esteroide 17-alfa-Hidroxilase/antagonistas & inibidores , Esteroide 17-alfa-Hidroxilase/sangue , Esteroide 17-alfa-Hidroxilase/genética , Superóxido Dismutase/sangue , Superóxido Dismutase/genética , Testosterona/sangueRESUMO
Polyphenols are natural compounds used by plants as a defense system against various stresses. In recent years, the importance of these polyhydroxyphenols has extensively increased due to their potent cardioprotection, anti-carcinogenic, anti-oxidant, anti-apoptotic, and anti-inflammatory properties. Therefore, various studies have reported promising results from the studies investigating their efficacy as a therapeutic strategy in various disorders such as human malignancies, cardiovascular diseases, nervous system impairments, diabetes, metabolic syndrome, aging, and inflammation-associated disorders, as well as a polycystic ovarian syndrome (PCOS). Since oxidative stress, hormonal, metabolic, and endocrine disturbances have been shown to play a crucial role in the initiation/progression of PCOS, polyphenols are suggested to be an effective treatment for this disorder. Therefore, this study aimed to discuss the therapeutic potential of multiple polyphenols in PCOS.
Assuntos
Produtos Biológicos/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Polifenóis/uso terapêutico , Feminino , HumanosRESUMO
Polycystic ovary syndrome is a common endocrine disorder worldwide. Recently, quercetin has been extensively investigated as a therapeutic option in patients with PCOS. Therefore, this study aimed to investigate the mechanisms underlying quercetin's positive effects by modulating key components of energy homeostasis and adipose tissue hormones in rats with letrozole-induced PCOS. Eighteen female Wistar rats were divided into three groups including control group (received carboxy methylcellulose (CMC 0.5%)), letrozole-induced PCOS ± quercetin group (received 1 mg/kg letrozole in CMC 0.5%), and letrozole-induced PCOS +/+ quercetin group (received same dose of letrozole + 100 mg/kg quercetin in CMC 0.5%). The estrous cycle, biochemical and hormonal parameters, as well as insulin resistance (IR) were evaluated in all groups. Western blotting was used to assess the expression levels of sirtuin-1 (SIRT-1), 5' AMP-activated protein kinase (AMPK), and adiponectin in target tissues of rats. The expression levels of visfatin and resistin were also evaluated through Real-time polymerase chain reaction (PCR). Treatment with quercetin improved the PCOS related disturbances in estrous cycle, lipid profile, serum levels of testosterone, estradiol and progesterone, and IR. Besides, the expression levels of AMPK and SIRT-1 in ovarian tissue were upregulated in the rats which received quercetin. Quercetin also reversed the PCOS-induced alteration in adipose tissue levels of adiponectin, visfatin, and resistin. Modulation of energy homeostasis through key components involved in this axis, as well as regulation of hormones releasing from adipose tissue may be the main underlying mechanisms for positive effects of quercetin in PCOS.
Assuntos
Proteínas Quinases Ativadas por AMP/efeitos dos fármacos , Síndrome do Ovário Policístico/tratamento farmacológico , Quercetina/uso terapêutico , Sirtuína 1/efeitos dos fármacos , Adiponectina/metabolismo , Animais , Ciclo Estral/efeitos dos fármacos , Feminino , Hormônios/sangue , Resistência à Insulina , Letrozol , Metabolismo dos Lipídeos/efeitos dos fármacos , Nicotinamida Fosforribosiltransferase/metabolismo , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/patologia , Ratos , Ratos Wistar , Resistina/metabolismoRESUMO
INTRODUCTION: Serum levels of several pro-inflammatory cytokines are higher in hemodialysis patients compared to healthy people. Curcumin has been shown to be able to decrease cytokines levels in nonuremic subjects. Our goal was to evaluate the effect of nanocurcumin administration on cytokines levels in hemodialysis patients. METHODS: The study was performed over a 3 months period on 54 hemodialysis patients who had been randomized to receive either nanocurcumin or placebo. Serum levels and gene expressions of tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) were evaluated using enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR). FINDINGS: Serum levels of IL-6 and TNF-α were similar in the two groups at baseline but were lower after 12 weeks of treatment with nanocurcumin compared to placebo (P = 0.024 for IL-6 and 0.02 for TNF). In the group given nanocurcumin, serum levels of both cytokines decreased substantially (P < 0.001 for each), whereas they were unchanged in the group given placebo. Gene expression for each cytokine in peripheral blood mononuclear cells (PBMCs) was reduced at 12 weeks vs. baseline in the group given nanocurcumin, and changes in gene expression correlated with changes in serum level for each of the two cytokines. DISCUSSION: The results indicate that nanocurcumin supplementation reduces both serum levels and gene expression of IL-6 and TNF-α in hemodialysis patients. The feasibility and potential clinical benefits of nanocurcumin treatment to reduce inflammation in hemodialysis patients warrant further study.
Assuntos
Leucócitos Mononucleares , Diálise Renal , Citocinas , Suplementos Nutricionais , Humanos , Inflamação/tratamento farmacológico , Diálise Renal/efeitos adversos , Fator de Necrose Tumoral alfaRESUMO
Cancer is considered as the main challenge of human communities, and it annually imposes a significant economic burden on society. Natural products have been used for treatment of many diseases including inflammation, infections, neurological disorders, atherosclerosis, asthma and cancer for many years. Sesquiterpene lactones (STLs) refers to a group of natural products with different biological activities. A type of STL that has recently attracted much attention is Alantolactone (ALT). In recent years, many studies have investigated the molecular mechanism of this compound affecting cancer cells and results suggest that this compound exerts its anticancer effects by providing free radicals and inhibiting some of the signaling pathways that are effective in progression of cancer cells. The present study is aimed to introduce the latest molecular mechanisms of ALT proposed by researchers in recent years.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Lactonas/farmacologia , Neoplasias/tratamento farmacológico , Sesquiterpenos de Eudesmano/farmacologia , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Humanos , Metástase Neoplásica , Neoplasias/metabolismo , Neoplasias/patologia , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de SinaisRESUMO
OBJECTIVE: The etiology of multiple myeloma (MM) is not known. Enzymes such as xanthine oxidase (XO) and NADPH oxidase 1 (NOX1) as relevant sources of reactive oxygen species (ROS) production may play a crucial role in the incidence and progress of MM. Uric acid generated by XO has a controversial dual role in both the prevention and promotion of cancer. We conducted a case-control study and selected patients with stage I MM to investigate the status of XO, NOX1, and uric acid in the patients and controls. METHODS: We used a sample of 33 patients with stage I MM and 30 healthy controls. The enzyme-linked immunosorbent assay (ELISA) measured the enzyme concentration of XO and NOX1, and the colorimetric method measured the serum level of uric acid. RESULTS: Mean serum levels for XO in patients and controls were 6.17±0.83 ng/ml and 4.12±0.57 ng/ml (P<0.001). serum levels of NOX1 were 4.35±1.03 ng/ml in patients and 3.54±0.91 ng/ml in controls (P<0.001). Evaluating the levels of XO and NOX1 in male and female populations showed a significant difference in the male population (NOX1 P=0.002; XO P<0.001) and female population (NOX1 P=0.002; XO P<0.001). Also, a significant correlation was observed between the two enzymes only in the female population (Pearson correlation=0.5; P=0.006). A significant inverse correlation found between albumin and XO (Pearson correlation=-0.7, P<0.001) and NOX1 (Pearson correlation=-0.5, P<0.001). XO was correlated with B2-m (Pearson correlation=0.37, P=0.003). There was no significant difference in uric acid between patients (6.2±1.2 mg/dl) and controls (5.7±1 mg/dl) (P=0.2), and no correlation was found with XO. CONCLUSION: The present study indicates the possible role of XO and NOX 1 in the etiology of MM. Although we found no correlation between uric acid and XO, further studies will help clarify the function of uric acid in the pathogenesis of MM.
.
Assuntos
Biomarcadores Tumorais/sangue , Mieloma Múltiplo/patologia , NADPH Oxidase 1/sangue , Ácido Úrico/sangue , Xantina Oxidase/sangue , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Estadiamento de Neoplasias , Espécies Reativas de Oxigênio/metabolismoRESUMO
Exosomes, as lipid nanostructure, are secreted by approximately all cell types within the body and actively involved in either short or long distances cell-cell communication in an autocrine and paracrine manner. Recently, exosomes are widely used as a nanocarrier for delivery of various nucleotide- or protein passed molecules including miRNA, and drugs into various cells, as a therapeutic strategy in a broad range of diseases including osteoarthritis. Osteoarthritis is one of the most common debilitating chronic musculoskeletal disorders with a multifaceted condition and an increasing impact on the quality of life. Therefore, this review aims to focus on the current knowledge of the exosomal miRNAs in the osteoarthritis to address their potential therapeutic application.
Assuntos
Complexo Multienzimático de Ribonucleases do Exossomo/genética , MicroRNAs/genética , Osteoartrite/genética , Complexo Multienzimático de Ribonucleases do Exossomo/fisiologia , Exossomos/genética , Exossomos/metabolismo , Humanos , MicroRNAs/metabolismo , Osteoartrite/fisiopatologia , Osteoartrite/terapiaRESUMO
OBJECTIVE: Multiple myeloma (MM) remains an incurable disease that needs better recognition and further research. Previous studies elucidated the interaction between myeloma cells and showed the necessity of bone marrow stromal cells for the initiation and progression of MM. Many chemokines and their receptors including interleukin-8 (IL-8) and soluble interleukin-6 receptor (sIL-6R) play important roles in this interaction. The main purpose of this study is evaluating the serum level of IL-8 and sIL-6R on stage-I of MM patients and healthy controls. METHODS: Serum samples from 30 stage-I MM patients (13 males and 17 females) and 30 healthy subjects as controls (13 males and 17 females) were examined in this study. The protein concentrations of serum IL-8 and sIL-6R were assessed by enzyme-linked immunosorbent assay (ELISA). RESULTS: The mean level of IL-8 and sIL-6R were significantly elevated in stage-I MM. The mean levels of IL-8 were 1246.57±279.22 ng/ml in stage-I MM and 902.53± 294.61 ng/ml in controls (P<0.001). The mean levels of sIL-6R were 5.39±1.38 ng/ml and 4.1±1.14 ng/ml in stage-I MM and controls, respectively (P<0.001). The mean levels of IL-8 were 1342.18±193.4 ng/ml in patient females and 859± 278.2ng/ml in control females (P <0.001). The mean levels of sIL-6R were 5.21±1.55 ng/ml and 3.91±1.22 ng/ml in patient females and control females, respectively (P=0.01). The mean level of sIL-6R in patient males and control males were 5.63±1.43 ng/ml and 4.34±1.04 ng/ml, respectively (P=0.01). A significant correlation (Pearson's correlation = 0.45, P=0.008) was observed in the population of females (patients and controls). CONCLUSION: The results of study suggest the possible involvement of IL-8 and the sIL-6R at stage-I MM and can better characterize the role of chemokines and their receptors in the disease process, especially in the early stages.
Assuntos
Biomarcadores Tumorais/sangue , Interleucina-8/sangue , Mieloma Múltiplo/sangue , Mieloma Múltiplo/diagnóstico , Receptores de Interleucina-6/sangue , Idoso , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de NeoplasiasRESUMO
BACKGROUND AND PURPOSE: Cancer stem cells (CSCs), as the subpopulation of cancer cells, are associated with carcinogenesis, chemoresistance, and metastasis in malignancies. Also, CSCs are considered as the major reason for treatment failure in prostate cancer (PCa). Alantolactone (ALT), exerts anticancer activity in different types of cancers. In the present study, the relationship between ALT and CSCs in PCa metastasis and the molecular mechanisms involved in the progression of PCa were investigated. EXPERIMENTAL APPROACH: In this study, to evaluate cell viability, MTT assay was performed. Then, PC3 cells were treated with nontoxic concentrations of ALT and after this step wound-healing assay, colony-formation assay and chemosensitization assay were applied to determine cell migration, the ability of colony formation, and chemoresistance, respectively. Also, real-time polymerase chain reaction and western blotting were used for the determination of genes and protein expression, respectively. FINDINGS/RESULTS: Our finding showed that ALT at nontoxic concentrations (0.01 and 0.1 µM) for 72 h suppressed the STAT3 phosphorylation and signaling pathway. Also, ALT was able to modulate the stemness of PCa cells through downregulation of expression of SOX2, Oct-4, Nanog, CD133, CD44, and upregulation of p53 expression. On the other hand, we further found that ALT in nontoxic concentrations sensitized PCa cells to cisplatin. CONCLUSION AND IMPLICATIONS: ALT combated the stemness of cancer cells and metastasis by antagonizing of STAT3 signaling pathway. In addition, ALT exhibited anti-metastatic properties and may have potential as a new chemotherapy agent for the reduction of PCa metastasis.
RESUMO
Purpose: Dihydropyrimidine dehydrogenase (DPD) is the principal enzyme in the catabolism of fluoropyrimidine drugs including capecitabine. A recent report has suggested that oxaliplatin chemotherapy is associated with elevated DPD levels and chemoresistance pattern. As a newly developed chemotherapeutic agent, 17-allyloamino-17-demethoxy-geldanamycin (17-AAG) can be effective in combination therapy with oxaliplatin and capecitabine in colorectal cancer (CRC). DPD expression level can be a predictive factor in oxaliplatin and capecitabine-based chemotherapy. We evaluated DPD in mRNA and protein levels with new treatments: 17-AAG in combination with oxaliplatin and capecitabine in HT-29 and HCT-116 cell lines. Methods: Drug sensitivity was determined by the water-soluble tetrazolium-1 assay in a previous survey. Then, we evaluated the expression levels of DPD and its relationship with the chemotherapy response in capecitabine, oxaliplatin, and 17-AAG treated cases in single and combination cases in two panels of CRC cell lines. DPD gene and protein expression levels were determined by real-time polymerase chain reaction and western blotting assay, respectively. Results: DPD gene expression levels insignificantly increased in single-treated cases versus untreated controls in both cell lines versus controls. Then, the capecitabine and oxaliplatin were added in double combinations, where DPD gene and protein expression increased in combination cases compared to pre-chemotherapy and single drug treatments. Conclusion: The elevated levels of cytotoxicity in more effective combinations could be related to a different mechanism apart from DPD mediating effects or high DPD level in the remaining resistance cells (drug-insensitive cells), which should be investigated in subsequent studies.
RESUMO
The purpose of this study was to clarify the mechanisms of the protective effects of low-dose sodium nitrite (SN) on oxygen and glucose deprivation (OGD)-induced endoplasmic reticulum (ER) stress in PC12 cells. The PC12 cells were exposed to 4 h of OGD and treated with 100 µmol SN. The expression and activity of ER stress markers, including PKR-like endoplasmic reticulum kinase (PERK), transcription factor 6 (ATF6), CCAAT/enhancer binding protein homologous protein (CHOP), as well as caspase-12 and -3, were detected by immunoblotting assay. Fluorescence staining was used to detect the levels of reactive oxygen species (ROS) and Ca2+ release from the ER. Cell viability was also evaluated by MTT assay. It was found that SN significantly inhibited ROS production and Ca2+ release from the ER in OGD-injured PC12 cells. Moreover, ER stress marker expression and cleaved fragments of caspase-3 and -12 in OGD-injured PC12 cells were decreased after SN treatment. These findings were accompanied by a significant increase in cell viability. It seems that SN exerts a neuroprotective effect at least partially through reduction of ROS-mediated ER stress caused by OGD insult.
RESUMO
Thyroid dysfunction is associated with elevated cardiovascular risk factors and atherosclerosis. It could be suggested that, hyperthyroidism is related to a higher prevalence of arterial abnormalities. Therefore, evaluating the endothelial dysfunction (ED) related biomarkers seem to be an important issue. It is not clear whether endothelial cells are biologically responsive to thyroid hormones (THs) or how THs induces the production of endothelial cells (EC)-derived proinflammatory mediators. Hence, in this study the effects of thyroxine (T4) on ED and inflammatory related mediators were evaluated. Human umbilical vein endothelial cells was used as endothelial cell model which was treated with concentrations of 50, 100, 200 nmol/L of T4 in various exposure times. In the following, gene and protein expression levels of EC-related markers including intercellular adhesion molecule-1 (ICAM-1), vascular endothelial growth factor (VEGF), and E-selectin were determined using real time polymerase chain reaction (RT-PCR) and western blotting methods. Also, interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) protein levels as proinflammatory cytokines were determined by enzyme linked immunosorbent assay (ELISA) method. Gene and protein expression analysis revealed that T4 treatments up regulated the levels of VEGF, ICAM-1, and E-selectin as ED markers. In addition, T4-treated cells had higher significant levels of IL-6 and TNF-α versus untreated cells in different incubation times. This study proposed the atherosclerotic effects of thyroid hormone. Based on our findings, T4 had strong effects on the gene and protein expression levels of pro-inflammatory, angiogenesis, and ED major mediators associated with atherosclerosis development.