RESUMO
Sodium-glucose co-transporter-2 (SGLT2) inhibitors, known as Gliflozins, are a class of Glucose-lowering drugs in adults with type 2 diabetes (T2D) that induce glucosuria by blocking SGLT2 co-transporters in the proximal tubules. Several lines of evidence suggest that SGLT2 inhibitors regulate multiple mechanisms associated with the regulation of varying cellular pathways. The 5'-adenosine monophosphate-activated protein kinase (AMPK) pathway plays an important role in metabolic homeostasis by influencing cellular processes. Recently, it has been shown that SGLT2 inhibitors can affect the AMPK pathway in differing physiological and pathological ways, resulting in kidney, intestinal, cardiovascular, and liver protective effects. Additionally, they have therapeutic effects on nonalcoholic fatty liver disease and diabetes mellitus-associated complications. In this review, we summarize the results of studies of AMPK-associated therapeutic effects of SGLT2 inhibitors in different organelle functions.
Assuntos
Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose , Adulto , Humanos , Proteínas Quinases Ativadas por AMP , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Transportador 2 de Glucose-Sódio , Glucose , ZeladoriaRESUMO
Multiple sclerosis (MS) is a life-threading disease that poses a great threat to the human being lifestyle. Having said extensive research in the realm of underlying mechanisms and treatment procedures, no definite remedy has been found. Over the past decades, many medicines have been disclosed to alleviate the symptoms and marking of MS. Meanwhile, the substantial efficacy of herbal medicines including curcumin must be underscored. Accumulated documents demonstrated the fundamental role of curcumin in the induction of the various signaling pathways. According to evidence, curcumin can play a role in mitochondrial dysfunction and apoptosis, autophagy, and mitophagy. Also, by targeting the signaling pathways AMPK, PGC-1α/PPARγ, and PI3K/Akt/mTOR, curcumin interferes with the metabolism of MS. The anti-inflammatory, antioxidant, and immune regulatory effects of this herbal compound are involved in its effectiveness against MS. Thus, the present review indicates the molecular and metabolic pathways associated with curcumin's various pharmacological actions on MS, as well as setting into context the many investigations that have noted curcumin-mediated regulatory effects in MS.
RESUMO
Hyperglycaemia is a major cause of pathophysiological processes such as oxidative stress, inflammation, and apoptosis in diabetes. Dapagliflozin (DAPA), a novel hypoglycaemic drug, has been shown to have anti-apoptotic, anti-inflammatory, and antioxidant effects in multiple experimental studies. In this study, we investigated the protective effects of DAPA in the hyperglycaemic condition to identify associated molecular mechanisms. human umbilical vein endothelial cells (HUVEC) endothelial cells were treated with 40 mM glucose for 72 h to establish an in vitro high glucose (HG) condition model, and then additional groups co-treated with or without DAPA before glucose treatment. Then, cell viability, reactive oxygen species (ROS), pro-inflammatory cytokines (IL-6 and TNF-α), apoptosis, and SIRT1 expression were measured. The results showed that DAPA pretreatment resulted in increased cell viability. Additionally, DAPA pretreatment decreased endothelial ROS, IL-6, and TNF-α levels in endothelial cells subjected to HG conditions. Moreover, DAPA pretreatment significantly prevented HG-induced apoptosis and caspase-3 activity in HUVECs. Furthermore, DAPA increased the expression of SIRT1, PGC-1α, and increased the phosphorylation levels of AMPK (p-AMPK) in a set of HG conditions in HUVECs. However, the endothelial protective effects of DAPA were abolished when cells were subjected to the SIRT1 inhibitor (EX-527) and AMPK inhibitor (Compound C). These findings suggest that DAPA can abrogate HG-induced endothelial cell dysfunction by AMPK/SIRT1 pathway up-regulation. Therefore, suggesting that the activation of AMPK/SIRT1 axis by DAPA may be a novel target for the treatment of HG-induced endothelial cell injury.
Assuntos
Hiperglicemia , Sirtuína 1 , Proteínas Quinases Ativadas por AMP/metabolismo , Anti-Inflamatórios/farmacologia , Apoptose , Compostos Benzidrílicos , Glucose/metabolismo , Glucosídeos , Células Endoteliais da Veia Umbilical Humana , Humanos , Hiperglicemia/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interleucina-6/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Sirtuína 1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
miRNAs are evolutionarily conserved non-coding ribonucleic acids with a length of between 19 and 25 nucleotides. Because of their ability to regulate gene expression, miRNAs have an important function in the controlling of various biological processes, such as cell cycle, differentiation, proliferation, and apoptosis. Owing to the long-standing regulative potential of miRNAs in tumor-suppressive pathways, scholars have recently paid closer attention to the expression profile of miRNAs in various types of cancer. Melatonin, an indolic compound secreted from pineal gland and some peripheral tissues, has been considered as an effective anti-tumor hormone in a wide spectrum of cancers. Furthermore, it induces apoptosis, inhibits tumor metastasis and invasion, and also angiogenesis. A growing body of evidence indicates the effects of melatonin on miRNAs expression in broad spectrum of diseases, including cancer. Due to the long-term effects of the regulation of miRNAs expression, melatonin could be a promising therapeutic factor in the treatment of cancers via the regulation of miRNAs. Therefore, in this review, we will discuss the effects of melatonin on miRNAs expression in various types of cancers.
Assuntos
Melatonina , MicroRNAs , Neoplasias , Apoptose/genética , Humanos , Melatonina/farmacologia , MicroRNAs/genética , Neoplasias/tratamento farmacológico , Neoplasias/genéticaRESUMO
Darwin, in the pangenesis theory, imagined particles, named as 'gemmules', which are released from all ('pan') cells of the body. By cell-cell communication and also circulation through the body, they finally reach the germ cells to participate in the generation ('genesis') of the new individual. It has been shown that circulatory exosomes are affected by environmental stressors and they can reach the parental germ cells. Therefore, in the mirror of his theory, circulatory exosomes could interact with epididymosomes: epididymis-derived exosomes which have a wide spectrum of variation in content and size, are very sensitive to environmental stressors, and may be involved in translating external information to the germ cells. The protein and RNA cargo would be transferred by epididymosomes to sperm during sperm maturation, which would be then delivered to the embryo at fertilization and inherited by offspring. Therefore, in this study, we will briefly discuss Darwin's pangenesis theory and its possible relation with epididymosomes. We believed that epididymosomes could be considered as an attractive candidate for the storage of RNA contents, changing the epigenome of the next generations, and allowing the reappearance acquired characteristics of ancestors. Therefore, epididymosomes, as a black box of Darwin's pangenesis, may unravel parental life history and also disclose the historical events that affect the life of offspring.
Assuntos
Evolução Biológica , Epididimo/fisiologia , Vesículas Extracelulares/fisiologia , Maturação do Esperma , Espermatozoides/fisiologia , Animais , Comunicação Celular , Epididimo/metabolismo , Epigenoma , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Hereditariedade , Humanos , Masculino , Transdução de Sinais , Espermatozoides/metabolismoRESUMO
OBJECTIVE: This current study evaluated the underlying mechanisms of LF against the inflammatory microRNAs (miRNAs), HMGB1 expression, and TLR4-MyD88-NF-кB pathway in LPS-activated murine RAW264.7 cells. METHODS: MTT assay was used to assess cell metabolism and the cell culture levels of the cytokines (TNF-α, IL-6) were evaluated by Enzyme-linked immunosorbent assay (ELISA). The expression of miRNAs was quantified by using qPCR and the expression of HMGB1, TLR4, MyD88, and phosphorylated NF-κB (P-p65) were determined with Western blot and qPCR, respectively. RESULTS: The results indicated that LF downregulates IL-6 and TNF-α expression. LF exhibited the degradation of P-p65 and reduced the production of HMGB1, TLR4, and MyD88 in LPS-induced inflammatory response. Importantly, in parallel with the suppression of cytokines and HMGB1-TLR4-MyD88-NF-кB pathway, LF could induce a decrease in inflammatory selected miRNAs, mmu-mir-155, and mmu-mir-146a expression. CONCLUSIONS: Altogether, these findings provide LF as a prominent anti-inflammatory agent that could modulate HMGB1, mmu-mir-155, mmu-mir-146a, and TLR4/MyD88/NF-кB pathway.
Assuntos
Proteína HMGB1/antagonistas & inibidores , Lactoferrina/farmacologia , MicroRNAs/antagonistas & inibidores , Fator 88 de Diferenciação Mieloide/antagonistas & inibidores , NF-kappa B/antagonistas & inibidores , Receptor 4 Toll-Like/antagonistas & inibidores , Animais , Relação Dose-Resposta a Droga , Expressão Gênica , Proteína HMGB1/biossíntese , Lipopolissacarídeos/toxicidade , Camundongos , MicroRNAs/biossíntese , Fator 88 de Diferenciação Mieloide/biossíntese , NF-kappa B/biossíntese , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Receptor 4 Toll-Like/biossínteseRESUMO
OBJECTIVE: Amnion membrane (AM) has been popular for the treatment of inflammatory disorders due to its cell repairing properties. This current study aims to find the underlying mechanisms of amnion membrane proteins (AMPs) against the pro-inflammatory miRNA, miR-155, miR-146, and anti-apoptotic microRNA, miR-21, in LPS-treated H9c2 cells. METHODS: Cell viability and apoptosis were determined by MTT assay and annexin V/PI staining. The production of the cytokines, TNF-α and IL-6 were evaluated by using qPCR and Enzyme-linked immunosorbent assay (ELISA), respectively. In addition, the expression of miRNAs was quantified by qPCR, and also the protein level of TLR4 and NF-kß was determined with western blotting. RESULTS: We found that AMPs ameliorated LPS-induced reduction of cell viability and augment apoptosis in H9c2 cells. AMPs efficiently inhibited cytokine expression (IL-6 and TNF-α) and activity of TLR4/NF-κB pathway in LPS-treated H9c2 cells. Correspondingly, in parallel with the suppression of pro-inflammatory cytokines and apoptosis, AMPs mitigated pro-inflammatory miRNA, miR-155 expression, while, the expression of miR-155 was found to be increased in LPS-treated H9c2 cells. Also, AMPs activated miR-146 expression in H9c2 cells under LPS treatment. Additionally, the elevated expression of miR-21 provoked by LPS was further enhanced by AMPs. CONCLUSIONS: In conclusion, AMPs could alleviate LPS-induced cardiomyocytes cells injury via up-regulation of miR-21, miR-146, and suppression of TLR4/NF-κB pathway, which plays a key role in the down-regulation of LPS-mediated miR-155 and inflammatory cytokine expression.
Assuntos
Âmnio/metabolismo , Mediadores da Inflamação/antagonistas & inibidores , MicroRNAs/antagonistas & inibidores , Miócitos Cardíacos/efeitos dos fármacos , NF-kappa B/antagonistas & inibidores , Receptor 4 Toll-Like/antagonistas & inibidores , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Células Cultivadas , Relação Dose-Resposta a Droga , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/toxicidade , MicroRNAs/biossíntese , Miócitos Cardíacos/metabolismo , NF-kappa B/biossíntese , Ratos , Receptor 4 Toll-Like/biossínteseRESUMO
Vitamin D3 efficacy against cardiovascular disease prevention has been reported in many experimental studies. We aimed to investigate the effect of the calcitriol or active form of Vitamin D3 (1, 25(OH) 2D3) on serum cholesteryl ester transfer protein (CETP) levels in a rabbit model of atherosclerosis. New Zealand white male rabbits were fed with 1% cholesterol diet and randomly assigned into two groups (n = 6). The case group was administrated with 50000 calcitriol (IU/kg/per wk) and the control group which administrated with calcitriol solvent (sesame oil) for 2 months. Then, after two months the lipid profile, CETP and 25OHD3 levels were measured. The serum concentration of CETP was increased after treatment with calcitriol in case group as compared to the control group (41.75 ± 3.19 vs. 34.5 ± 2.3, ng/ml, P < 0.05). We also observed higher levels of the 25OHD3 in the calcitriol group at the 1st month (16.3 ± 1.64 vs. 12.8 ± 1.33 ng/ml) and the 2nd month (19.5 ± 2.14 vs. 12.5 ± 1.25 ng/ml) as compared with the control group. the significant increase in the level of HDL-C was observed in the case group than the control group (P < 0.01). In addition, serum levels of LDL- Cholesterol (LDL-C), Triglyceride (TG) were reduced after assessment at 1st and 2nd month after administration of calcitriol. Our research indicated the significant anti-atherogenic effects of calcitriol in the rabbit model of atherosclerosis. However, increased in CETP levels by calcitriol may know as an additional way, which interfere with the anti-atherogenic effects of calcitriol.
Assuntos
Calcitriol , Proteínas de Transferência de Ésteres de Colesterol , Animais , Colesterol , HDL-Colesterol , Lipídeos , Masculino , Projetos Piloto , CoelhosRESUMO
Studies have shown that sulforaphane (SFN) has potent anti-inflammatory and free radical scavenging effects on obesity and associated disorder such as diabetes, polycystic ovary syndrome, and metabolic syndrome. fractalkine (CX3CL1) and its receptor, CX3CR1, play an important role in muscle metabolism by improving insulin-sensitizing effects. Here, in this study we examined the SFN effect on CX3CL1 and its receptor, CX3CR1, in C2C12 myotubes in palmitic acid (PA)-induced oxidative stress and inflammation. The results showed that PA (750 µM) evoked lipotoxicity as a reduction in cell viability, increased IL-6 and TNF-α expression, and enhanced reactive oxygen species (ROS). However, SFN pretreatment attenuated the levels of, IL-6 and TNF-α in C2C12 myotubes exposure to PA. Moreover, SFN pretreatment up-regulated nuclear factor erythroid related factor 2 (Nrf2) /heme oxygenase-1(HO-1) pathway protein in C2C12 cells as indicated by a decrease in ROS levels. Interestingly, PA also caused an increase in CX3CL1 and CX3CR1 expression that SFN abrogated it. We also found the protective effect of SFN agonist PA-induced lipotoxicity with promotes in UCP3 gene expression in C2C12 cells. Collectively, these findings suggest that SFN hampers the PA-induced inflammation in C2C12 cells by modulation of the Nrf2/HO-1 pathway and CX3CL1/CX3CR1 axis and may propose a new therapeutic approach to protect against obesity-associated disorders in skeletal muscle cells.
Assuntos
Receptor 1 de Quimiocina CX3C/metabolismo , Quimiocina CX3CL1/metabolismo , Isotiocianatos/farmacologia , Mioblastos Esqueléticos/metabolismo , Ácido Palmítico/toxicidade , Sulfóxidos/farmacologia , Animais , Linhagem Celular , Interleucina-6/metabolismo , Camundongos , Mioblastos Esqueléticos/patologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Protection of the cardiac cell against hypoxia-induced cell damage is one of the main approaches to preventing cardiovascular disease. Earlier studies have shown the cardioprotective effect of the human Amniotic Membrane (hAM) in animal model of cardiac injury. However, the effect of Amniotic Membrane Proteins (AMPs), extracted from hAM, on myocardial hypoxia injury remains unclear. So, our study aimed to investigate the protective effect of AMPs against hypoxia-induced cardiomyocytes apoptosis. H9c2 cardiomyocytes were pre-treated with AMPs followed by 24â¯h in hypoxia condition. Cell viability and apoptotic induction were detected by MTT and PI staining assay. Furthermore, the reactive oxygen species (ROS) generation, caspase-3 activity and malondialdehyde (MDA) were measured using the relevant kits. Moreover, apoptosis associated molecules and NF-kB p65 subunit, the master regulator of inflammation; expression was measured by western blotting. Our results indicated that AMPs increased the cellular viability of H9c2 cells during hypoxia and attenuated apoptotic induction. AMPs reduced hypoxia-induced ROS generation and as indicated by decreased MDA content. Moreover, AMPs decreased Bax/Bcl-2 ratios followed by reduction the caspase-3 activity; and further repressed the phosphorylated NF-kB p65. Altogether, suggesting that AMPs offers cardioprotective effects to H9c2 cell in hypoxia condition by modulating the gene involved in apoptosis and reducing oxidative stress and inflammatory response.
Assuntos
Âmnio/metabolismo , Apoptose/efeitos dos fármacos , Hipóxia/metabolismo , Proteínas de Membrana/metabolismo , Miócitos Cardíacos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Âmnio/química , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Humanos , Miócitos Cardíacos/patologiaRESUMO
Regarding post-complication of convenient therapies against breast cancer, the emergence of effective approaches is essential. Photodynamic therapy is touted as a novel invasive therapeutic approach by the application of a photosensitizer promoted by laser irradiation. This study aimed to investigate the combined regime of low-level laser irradiation with zinc phthalocyanine in human breast cancer ZR-75-1 cell line. Cells were treated with 0.01 and 5 µg/ml of ZnPc for 24 h and exposed to radiation (70 mW) for 60 s. Cell viability was evaluated by MTT and flow cytometry. Cell migration capacity was monitored by scratch test, Transwell migration insert, and gelatin zymography. The function of MDR in treated cells was examined by Rhodamine 123 exclusion test. The level of GALNT11 was measured by ELISA. The expression of Bax and Bcl-2 genes was evaluated by real-time PCR. Laser irradiation and zinc phthalocyanine induced cell cytotoxicity in a dose-dependent manner. Flow cytometry analysis showed the induction of apoptotic and necrotic changes in treated cells. We found a reduction in migration rate and MMP-9 activity in cells undergoing the experimental procedure (p < 0.05). Immunofluorescence imaging revealed the intracellular accumulation of Rhodamine 123 coincided with a reduction in the level of GALNT11 in treated cells, showing the reduction of MDR activity and tumor cell resistance. Similar to flow cytometry assay, the reduction of Bcl-2 (approximately twofold) and upregulation of Bax genes were found in treated cells. Photodynamic therapy could be as an effective and alternative method for the treatment of breast cancer in a human.
Assuntos
Neoplasias da Mama/patologia , Indóis/farmacologia , Luz , Compostos Organometálicos/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Apoptose/efeitos dos fármacos , Contagem de Células , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos , Isoindóis , Metaloproteinase 9 da Matriz/metabolismo , N-Acetilgalactosaminiltransferases/metabolismo , Necrose , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Rodamina 123/metabolismo , Compostos de Zinco , Proteína X Associada a bcl-2/metabolismoRESUMO
The main aim of the present study was to show the effect of bovineLactoferrin (bLF), an 80 kD iron-binding glycoprotein, its application on antioxidant esterase activities and 8-isoprostane changes in high-cholesterol-diet fed (HCD-Fed) rats. The 44 adult Sprague-Dawley male rats were randomly assigned into four experimental groups. They were randomly assigned into four equivalent groups (n = 11). The groups included the control group which was fed with normal diet, bLF group, the third group which were made hypercholesterolemia by being fed with high cholesterol diet, and the last group which consisted of hypercholesterolemia rats treated with bLF (HCD + bLF) for 4 weeks (200 mg.kg-1 per day wt. dissolved in 0.9% normal saline).After 4 weeks, the serum Paraoxonase1 (PON1), Arylesterase (ARE) activity and 8-isoprostane with lipid profile were measured. Upon treatment with the bLF, the decrease in LDL-Cholesterol (LDL-C), Glucoses, Triglyceride (TG) and Total-Cholesterol (TC) levels and an increase in HDL-Cholesterol (HDL-C) level were observed. The co-administration of bLf for 4 weeks had decreased the 8-isoprostane levels significantly (P < 0.001) (86.36 ± 7.1 vs 117.18 ± 8.62) when compared to hypercholesterolemia-induced rats. Also, the Atherogenic Index (AI) in HCD + bLF group showed a significant decrease as compared to the HCD group (P < 0.001) (0.37 ± 0.07 vs 0.57 ± 0.09). The results indicated that bLF was effective against oxidative stress by its ability to increase PON1 activity and reduce the lipid peroxidation in high-cholesterol-fed rats.
RESUMO
OBJECTIVES: Metastasis in breast cancer is the first cause of death in patients. The epidermal growth factor (EGF) increases cancer cells' invasion, and migration. Melatonin's inhibitory effects on various types of cancer were confirmed. This study aimed to investigate whether melatonin could apply its impact through the EGF-related pathways or not. METHODS: First, MDA-MB-231 and MCF7 cells were cultured, and then melatonin effects on cell viability were determined by MTT assay. Transwell invasion assay was applied to identify the invasiveness of these breast cancer cell lines under treatment of EGF and melatonin. Real-time RT-PCR then investigated the expression of MMP9 and MMP2 in determined groups. Cell proliferation was also assayed under EGF and melatonin treatment using Ki67 assessment by flow cytometry. RESULTS: The rate of invasion and migration of EGF-treated cells increased in both groups, in which melatonin caused increased invasion by EGF just in MCF7 cells. MMP9 and MMP2 expression increased significantly in both cell lines under EGF treatment, and melatonin increased these genes' expression in both cell lines (p<0.05). EGF increased the MMP9 and MMP2 gene expression, and melatonin increased EGF-induced expression (p<0.05). The EGF reduced the expression of the Ki67 protein in the MCF7 cell line, which was negatively affected by melatonin and EGF. In contrast, along with melatonin, EGF did not affect the proliferation of the MDA-MB-231 cell line. CONCLUSIONS: The results of this study show that melatonin in the presence of EGF does not show the anti-cancer properties previously described for this substance.
RESUMO
BACKGROUND: Dapagliflozin, a selective Sodium-glucose cotransporter-2 (SGLT2) inhibitor, has been shown to play a key role in the control and management of metabolic and cardiac diseases. OBJECTIVE: The current study aims to address the effects of dapagliflozin on the expression of fractalkine (FKN), known as CX3CL1, and its receptors CX3CR1, Nuclear factor-kappa B(NF-κB) p65 activity, Reactive oxygen species (ROS), and inflammation in LPS-treated H9c2 cell line. METHODS: H9c2 cells were cultured with lipopolysaccharide (LPS) to establish a model of LPS-induced damage, and then, subsequently were treated with dapagliflozin for 72 h. Our work included measurement of cell viability (MTT), Malondialdehyde (MDA), intracellular ROS, tumor necrosis factor-α (TNF-α), NF-κB activity, and expression of CX3CL1/CX3CR1. RESULTS: The results showed that LPS-induced reduction of cell viability was successfully rescued by dapagliflozin treatment. The cellular levels of MDA, ROS, and TNF-α, as an indication of cellular oxidative stress and inflammation, were significantly elevated in H9c2 cells compared to the control group. Furthermore, dapagliflozin ameliorated inflammation and oxidative stress through the modulation of the levels of MDA, TNF-α, and ROS. Correspondingly, dapagliflozin reduced the expression of CX3CL1/CX3CR1, NF-κB p65 DNA binding activity, and it also attenuated nuclear acetylated NF-κB p65 in LPS-induced injury in H9c2 cells compared to untreated cells. CONCLUSION: These findings shed light on the novel pharmacological potential of dapagliflozin in the alleviation of LPS-induced CX3CL1/CX3CR1-mediated injury in inflammatory conditions such as sepsis-induced cardiomyopathy.
Assuntos
Receptor 1 de Quimiocina CX3C , Quimiocina CX3CL1 , NF-kappa B , Animais , Compostos Benzidrílicos , Receptor 1 de Quimiocina CX3C/genética , Receptor 1 de Quimiocina CX3C/metabolismo , Quimiocina CX3CL1/genética , Quimiocina CX3CL1/metabolismo , Glucosídeos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição RelA , Fator de Necrose Tumoral alfaRESUMO
Exercise is considered to be a "medicine" due to its modulatory roles in metabolic disorders, such as diabetes and obesity. The intensity and duration of exercise determine the mechanism of energy production by various tissues of the body, especially by muscles, in which the requirement for adenosine triphosphate (ATP) increases by as much as 100-fold. Naturally, athletes try to improve their exercise performance by dietary supplementation with, e.g., vitamins, metabolites, and amino acids. MNAM, as a vitamin B3 metabolite, reduces serum levels and liver contents of triglycerides and cholesterol, and induces lipolysis. It stimulates gluconeogenesis and prohibits liver cholesterol and fatty acid synthesis through the expression of sirtuin1 (SIRT1). It seems that MNAM is not responsible for the actions of NNMT in the adipose tissues as MNAM inhibits the activity of NNMT in the adipose tissue and acts as an inhibitor of its activity.NNMT-MNAM axis is more activated in the muscles of individuals undergoing the high-volume-low-intensity exercise and caloric restriction. Therefore, MNAM could be an important myokine during exercise and fasting where it provides the required energy for muscles through the induction of lipolysis and gluconeogenesis in the liver and adipose tissues, respectively. Increased levels of MNAM in exercise and fasting led us to propose that the consumption of MNAM during training, especially endurance training, could boost exercise capacity and improve performance. Therefore, in this review, we shed light on the potential of MNAM as a dietary supplement in sports medicine.
Assuntos
Atletas , Suplementos Nutricionais , Colesterol , Humanos , Niacinamida/análogos & derivadosRESUMO
The role of cancer stem cells (CSCs) in cancer incidence, drug resistance, and relapse after chemotherapy has been discussed and it has been confirmed that CSCs are extremely important and so, are suitable for therapeutic targeting. Sox families play an important role in carcinogenesis and dis-regulation of SOXs molecules has been observed in different types of cancers. The members of this family have been shown to play an important role in the maintenance of CSCs. In this article, we have tried to evaluate the role of different family members in CSCs maintenance, review various studies in this field and provide a perspective view on this issue. Also, due to the important role and many studies in the field of SOX2 molecule in CSCs, we try to have more focus on this molecule and examine the potential of these molecules for therapeutic targeting.
Assuntos
Células-Tronco Neoplásicas/metabolismo , Fatores de Transcrição SOXB1/metabolismo , Carcinogênese/metabolismo , Humanos , Células-Tronco Neoplásicas/fisiologia , Fatores de Transcrição SOXB1/análise , Fatores de Transcrição SOXB1/genéticaRESUMO
OBJECTIVE: This study aimed to show the long-term results in patients who underwent unidirectional valve patch repair of ventricular septal defect with pulmonary artery hypertension. METHODS: Thirty-five acyanotic patients aged 2 to 26 years (mean 9.3 years) with a large ventricular septal defect and elevated pulmonary vascular resistance (mean 9.5 Wood units) underwent surgery in Madani Heart Hospital. The medical records and clinical outcomes were reviewed from March 1998 to March 2017. RESULTS: Five patients died in the first postoperative week. In the long-term follow-up (mean 11 years), two patients were lost to follow-up. Pulmonary artery hypertension gradually decreased in 17 patients within 6-12 months with significant improvement in right ventricular end-diastolic diameter, New York Heart Association functional class, and tricuspid regurgitation. Eleven patients with persistent pulmonary artery hypertension were divided into tolerable and non-tolerable groups. Six patients in the tolerable group had satisfactory conditions compared to before the operation, and gained weight with improved functional class despite echocardiographic findings of persistent elevated pulmonary artery pressure. One had a full-term delivery by caesarean section in the fifth postoperative year. Five patients in the non-tolerable group gradually developed right heart failure and complications such as extremity edema, ascites, pleural effusions, and died after 10-30 months. CONCLUSION: Although relatively high mortality occurred during long-term follow-up, surviving patients were in a better condition and functional class despite persistent pulmonary artery hypertension. Therefore, fear of persistent pulmonary artery hypertension should not prohibit surgery in this group of patients.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Comunicação Interventricular/cirurgia , Hipertensão Arterial Pulmonar/fisiopatologia , Artéria Pulmonar/fisiopatologia , Adolescente , Adulto , Pressão Arterial , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/mortalidade , Criança , Pré-Escolar , Progressão da Doença , Feminino , Comunicação Interventricular/diagnóstico por imagem , Comunicação Interventricular/mortalidade , Comunicação Interventricular/fisiopatologia , Humanos , Masculino , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/fisiopatologia , Hipertensão Arterial Pulmonar/diagnóstico , Hipertensão Arterial Pulmonar/mortalidade , Circulação Pulmonar , Recuperação de Função Fisiológica , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Resistência Vascular , Adulto JovemRESUMO
OBJECTIVES: The changes in testosterone level and its correlation with the endothelial nitric oxide systems balance in patients with coronary artery disease (CAD) remains uncertain. Therefore, in our study, we aimed to evaluate the levels of testosterone, endothelin-1 (ET-1), nitric oxide (NO), and endothelial NOS (eNOS) in CAD patients, and control group to find the relationship between these parameters and disease severity. METHODS: Forty-four patients as CAD group with significant (≥50%) stenosis confirmed by angiography was included in the study, and 40 healthy men were included as the control group. According to the number of vessels obstruction, CAD severity was determined. The serum indicated parameters were assessed to discriminate between patients and controls. RESULTS: It was found that testosterone levels in the CDA group were significantly lower than those of the control group (p<0.05). In addition, the level of ET-1 in the CAD group was higher than that in the control group, but levels of NO and eNOS in observation were significantly lower than those in the control group (p<0.05). The correlation analysis revealed that testosterone was passivity correlated with serum NO levels (r=0.550, p=0.001). CONCLUSIONS: The current study reports that serum levels of testosterone are closely related to endothelial NO levels and might be of relevance to the pathogenesis of endothelial dysfunction and disease severity in CAD patients.
Assuntos
Doença da Artéria Coronariana , Endotelina-1 , Óxido Nítrico Sintase Tipo III , Óxido Nítrico , Testosterona , Doença da Artéria Coronariana/sangue , Endotelina-1/sangue , Humanos , Masculino , Óxido Nítrico/sangue , Óxido Nítrico Sintase Tipo III/sangue , Índice de Gravidade de Doença , Testosterona/sangueRESUMO
Introduction: Cardiovascular system is highly sensitive to LPS-induced oxidative damage. This study aimed to show the inhibitory effect of bacterial Lipase on LPS-induced cardiomyoblasts toxicity. Methods: Rat cardiomyoblasts H9C2 were classified into Control, LPS (cells received 0.1, 1 and 10 µg/mL LPS) and LPS+ Lipase groups. In LPS+Lipase group, different concentrations of lipopolysaccharide were pre-incubated with 5 mg/mL bacterial lipase at 37ËC overnight prior to cell treatment. After 72 hours, cell viability was assessed by MTT assay. The expression of key genes related to toll-like receptor signaling pathways was assessed by real-time PCR assay. Percentage of fatty acids was evaluated in each group using gas chromatography assay. The levels of NO was also measured using the Griess reaction. Results: Data showed H9C2 cells viability was decreased after exposure to LPS in a dose-dependent manner (P < 0.05). Incubation of LPS with lipase increased cell survival rate and closed to near-to-control levels (P < 0.05). Lipase had the potential to blunt the increased expression of IRAK and NF-κB in cells after exposure to the LPS. Compared to the LPS group, lipase attenuated the increased level of NO-induced by LPS (P < 0.05). Gas chromatography analysis showed the reduction of saturated fatty acids in cells from LPS group while the activity of lipase prohibited impact of LPS on cell fatty acid composition. LPS decreased the ability of cardiomyoblasts to form colonies. Incubation of LPS with lipase enhanced clonogenic capacity. Conclusion: Reduction in lipopolysaccharide-induced cytotoxicity is possibly related to lipase activity and reduction of modified lipopolysaccharide with toll-like receptor.
RESUMO
Ovarian aging occurs due to the reduction of the quality and quantity of the oocytes, and is regulated by mitochondrial survival and apoptotic signals. Reactive Oxygen Species (ROS) are one of those signals considered detrimental to cellular homeostasis. Nowadays, ROS are regarded as a regulatory factor at low levels as it induces the stress resistance which in turn increases the longevity. It is believed that the main mechanism for the life-promoting role of the ROS mediated by the 5' Adenosine Monophosphate-activated Protein Kinase (AMPK). N1-Methylnicotinamide (MNAM) is well known for its anti-diabetic, anti-thrombotic, and anti-inflammatory activity. Aldehyde oxidase 1 (AOX1) is a detoxifying enzyme, which metabolizes the MNAM and produces two metabolites including N1-methyl-2-pyridone-5- carboxamide (2py) and N1-methyl-4-pyridone-3-carboxamide (4py). The activity of AOX1 enhances the production of ROS and improves the longevity. It has been reported that the MNAM could postpone the aging through the induction of low-level stress. It has been documented that the production of MNAM is significantly higher in the cumulus cells of the patients with Polycystic Ovary Syndrome (PCOS) and its administration on the rat model of PCOS has been shown to alleviate the hyperandrogenism and successfully activate the ovarian AMPK. Therefore, it can be hypothesized that the anti-ovarian aging effects of the MNAM are possibly based on the activation of AMPK through transient elevation of the ROS.