جستجوی مقالات مرتبط با کلیدواژه « autophagy » در نشریات گروه « پزشکی »
-
Objective (s)
This study investigated the inhibitory effect of apatinib on lung cancer cells with high expression of vascular endothelial growth factor-2 (VEGFR-2) and on inducing cellular autophagy and drug resistance.
Materials and MethodsThe expression of VEGFR-2 was detected using western blotting and RT-PCR. Cell proliferation was measured using the CCK8 and colony formation assays. The cell apoptosis rate was determined using flow cytometry and tunnel assay. Cellular autophagy was detected by measuring the expression of LC3-II using Western blotting and cellular immunofluorescence. The inhibitory effect of apatinib on lung cancer cells and transplanted tumors was observed after treatment with the autophagy inhibitor chloroquine.
ResultsApatinib dose-dependently inhibited the proliferation of H1975 and H446 cells; it induced apoptosis via the PARP and caspase 3 pathways in H1975 and H446 cells and effectively inhibited the growth of transplanted tumors. Apatinib induced autophagy in a dose-dependent manner in H1975 and H446 cells. The inhibitory effect of apatinib on cells and the promotion of apoptosis were significantly enhanced after treatment with chloroquine. Immunohistochemistry showed that combining apatinib with chloroquine could reduce the expression of CD31 and Ki67 and increase the expression of caspase 3.
ConclusionApatinib inhibits proliferation and induces apoptosis in H1975 and H1446 lung cancer cells with high VEGFR2 expression and autophagy in H1975 and H446 cells.
Keywords: Apatinib Mesylate, Apoptosis, Autophagy, Lung Neoplasms, Cell Proliferation, VEGFR2} -
Objective (s)
Gefitinib (GEF) is a targeted medicine used to treat locally advanced or metastatic non-small cell lung cancer (NSCLC). However, GEF’s hepatotoxicity limits its clinical use. This study aims to investigate the protective effect of naringin (NG) against GEF-induced hepatotoxicity.
Materials and MethodsFifty female ICR mice were randomly divided into 5 groups: Control, GEF (200 mg/kg), NG (50 mg/kg) + GEF (200 mg/kg), NG (100 mg/kg) +GEF (200 mg/kg), NG (200 mg/kg) +GEF (200 mg/kg). After 4 weeks of continuous administration, the mice were euthanized. The blood and liver tissue samples were collected.
ResultsThe results indicated that the GEF group showed increased liver index, liver enzyme activities, and decreased glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activities. Some hepatocytes showed hydropic degeneration and focal necrosis. Cell apoptosis, Cleaved-caspase3, and Poly (ADP-ribose) polymerase 1 (PARP1) increased. Transmission electron microscopy revealed the presence of numerous autophagic lysosomes or autophagosomes around the cell nucleus. Compared to the GEF group, NG can reverse these changes.
ConclusionIn summary, NG alleviates GEF-induced hepatotoxicity by anti-oxidation, inhibiting cell apoptosis, and autophagy. Therefore, this study suggests the use of NG to mitigate GEF’s toxicity to the liver.
Keywords: Apoptosis, Autophagy, Gefitinib, Hepatotoxicity, Naringin} -
Introduction
Aging affects cardiac function and heart output. Regular exercise can improve heart function in old age. This experimental study evaluated the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on cardiomyocyte autophagy and cardiac function.
MethodsIn this study, 24 older male Wistar rats (>20 months) were divided into three groups of Control, HIIT, and MICT. The animals in the control group received no training, while the HIIT and MICT groups performed high and moderate training intensities at different intervals. Aerobic power and training capacity (VO2max) were also assessed before the training. After eight weeks of training (5 days/week), two-dimensional echocardiography was used for the sonographic assessment of the heart, and the tissue samples of the left ventricle were dissected for assessing gene expression (PGC-1α and FOXO-3α). Data were analyzed using SPSS software, version 19 and presented using Mean±SD. P<0.05 was considered as statistically significant.
ResultsThe expression of the PGC-1α gene significantly increased, while the FOXO-3α gene expression significantly decreased in the HIIT and MICT groups compared to the control animals (p<0.05). Left ventricle end-systolic dimension decreased (p<0.05), while the left ventricular end-diastolic diameter, ejection fraction, and fractional shortening increased (p<0.05) in the training groups compared to the control animals. These changes were also significant in the HIIT group compared to the MICT group (p<0.05)
ConclusionHIIT can reduce the expression of autophagy genes and improve cardiac function in aged heart more than MICT.
Keywords: High-Intensity Interval Training (HIIT), Moderate-Intensity Continuous Training (MICT), Autophagy, FOXO3-3Α, PGC-1Α, Aged Heart} -
We recently have read with great interest an article entitled “The Potential Role of Autophagy in Progression of Liver Fibrosis in Chronic Hepatitis B Patients Receiving Antiviral Treatment: A Brief Report”, by Lankarani and others, which was published in your esteemed journal (IJMS Volume 49, Issue 3, March 2024).
Keywords: Autophagy, Liver Cirrhosis, Beclin-1} -
Purpose
Among varied ω-3 polyunsaturated fatty acid types, the therapeutic properties of docosahexaenoic acid (DHA) have been indicated under diabetic conditions in different cell lineages. Here, we investigated the anti-diabetic properties of DHA in rats with type 2 diabetes mellitus (D2M) focusing on autophagy-controlling factors.
MethodsD2M was induced in male Wistar rats using a single dose of streptozocin (STZ) and a high-fat diet for 8 weeks. On week 2, diabetic rats received DHA 950 mg/kg/d until the end of the study. After that, rats were euthanized, and aortic and cardiac tissue samples were stained with H&E staining for histological assessment. The expression of adhesion molecules, ICAM-1 and VCAM-1, was measured in heart samples using real-time PCR analysis. Using western blotting, protein levels of BCLN1, LC3, and P62 were measured in D2M rats pre- and post-DHA treatment.
ResultsData showed intracellular lipid vacuoles inside the vascular cells, and cardiomyocytes, after induction of D2M and DHA reduced intracellular lipid droplets and in situ inflammatory response. DHA can diminish increased levels of ICAM-1 in diabetic conditions (PControl vs. D2M rats=0.005) and reach near-to-control values (PControl vs. D2M rats=0.28; PD2M rats vs. D2M rats+DHA=0.033). Based on western blotting, D2M slightly increased the BCLN1 and LC3-II/I ratio without affecting P62. DHA promoted the LC3II/I ratio (P=0.303) and reduced P62 (PControl vs. D2M rats+DHA =0.0433; pD2M vs. D2M rats+DHA=0.096), leading to the completion of autophagy flux under diabetic conditions.
ConclusionDHA can reduce lipotoxicity of cardiovascular cells possibly via the activation of adaptive autophagy response in D2D rats.
Keywords: Diabetes Mellitus, Endothelial Cells, Vascular System Injuries, Docosahexaenoic Acid, Autophagy, Rats} -
ObjectiveAutophagy, as a cellular pathway involved inremoving damaged proteins and organelles, performs a vitalfunction in the homeostasis and fate of cells. Natural compoundsof coumarin (CO) are found in a variety of herbs. Due to theirmany medicinal properties, including antitumor and antiproliferative activity, they are involved in apoptosis and autophagyprocesses. This investigation desired to analyze the apoptotic andautophagic effects of p-coumaric acid (PCA) and CO on HT-29cells cultured in fibrin hydrogel.Materials and MethodsCell viability and apoptotic andautophagic changes were evaluated by MTT assay, AcridineOrange, 4′,6-diamidino-2-phenylindole (DAPI), andmonodansylcadaverine (MDC) staining. The expression Bax, Bad,Bcl2, Lc3, Beclin-1, P53 and Atg5 was respectively measured byqRT-PCR and Western blotting.ResultsCO (IC50=25 μM) and PCA (IC50=150 μM) had a doseand time-dependent cytotoxic effect in HT-29 cells. So, thecytotoxic effects of CO were significantly higher than PCA andthese differences were also evident in cell morphologyinvestigations. The data illustrated a high expression of proapoptotic and pro-autophagic genes and a declined expression ofanti-apoptotic and anti-autophagic genes.ConclusionCO (that was more potent) and p-coumaric acidinduced autophagy via PI3K/Akt/mTOR and AMPK/mTORsignaling on HT-29 cells.Keywords: Autophagy, Cancer Phytotherapy, Coumarin, Signaling Pathway}
-
Objective (s)
To investigate whether 3-methyladenine (3-MA) can protect the kidney of streptozotocin (STZ) - induced diabetes mice, and explore its possible mechanism.
Materials and MethodsSTZ was used to induce diabetes in C57BL/6J mice. The mice were divided into normal control group (NC), diabetes group (DM), and diabetes+3-MA intervention group (DM+3-MA). Blood glucose, water consumption, and body weight were recorded weekly. At the end of the 6th week of drug treatment, 24-hour urine was collected. Blood and kidneys were collected for PAS staining to evaluate the degree of renal injury. Sirius red staining was used to assess collagen deposition. Blood urea nitrogen (BUN), serum creatinine, and 24-hour urine albumin were used to evaluate renal function. Western blot was used to detect fibrosis-related protein, inflammatory mediators, high mobility group box 1 (HMGB1)/NF-κB signal pathway molecule, vascular endothelial growth factor (VEGF), and podocin, and immunohistochemistry (IHC) was used to detect the expression and localization of autophagy-related protein and fibronectin.
ResultsCompared with the kidney of normal control mice, the kidney of diabetes control mice was more pale and hypertrophic. Hyperglycemia induces renal autophagy and activates the HMGB1/NF-κB signal pathway, leading to the increase of inflammatory mediators, extracellular matrix (ECM) deposition, and proteinuria in the kidney. In diabetic mice treated with 3-MA, blood glucose decreased, autophagy and HMGB1/NF-κB signaling pathways in the kidneys were inhibited, and proteinuria, renal hypertrophy, inflammation, and fibrosis were improved.
Conclusion3-MA can attenuate renal injury in STZ-induced diabetic mice through inhibition of autophagy and HMGB1/NF-κB signaling pathway.
Keywords: 3-Methyladenine, Autophagy, Diabetes, Diabetic nephropathy, HMGB1, NF-κB signaling - pathway} -
Objective (s)
Cervical cancer (CC) is the most common gynecological malignant tumor and the fourth leading cause of cancer-related death in women. The progression of CC is significantly affected by autophagy. Our objective was to use bioinformatics analysis to explore the expression, prognostic significance, and immune infiltration of autophagy-related genes in CC.
Materials and MethodsWe identified a set of autophagy-related differentially expressed genes (ARDEGs) from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. ARDEGs were further validated by The Human Protein Atlas (HPA), GSE52903, and GSE39001 dataset. Hub genes were found by the STRING network and Cytoscape. We performed Gene Set Enrichment Analysis (GSEA), Gene ontology analysis (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and immune infiltration analysis to further understand the functions of the hub genes. Kaplan-Meier (K-M) and receiver operating characteristic (ROC) were used to check the hub genes.
ResultsA total of 10 up-regulated (CXCR4, BAX, SPHK1, EIF2AK2, TBK1, TNFSF10, ITGB4, CDKN2A, IL24, and BIRC5) and 19 down-regulated (PINK1, ATG16L2, ATG4D, IKBKE, MLST8, MAPK3, ERBB2, ULK3, TP53INP2, MTMR14, BNIP3, FOS, CCL2, FAS, CAPNS1, HSPB8, PTK6, FKBP1B , and DNAJB1) ARDEGs were identified. The ARDEGs were enriched in cell growth, apoptosis, human papillomavirus infection, and cytokine-mediated. Then, we found that low expression of MAPK3 was associated with poor prognosis in CC patients and was significantly enriched in immune pathways. In addition, the expression of MAPK3 was significantly positively correlated with the infiltration levels of macrophages, B cells, mast cell activation, and cancer-associated fibroblasts. Furthermore, MAPK3 was positively correlated with LGALS9, and negatively correlated with CTLA4 and CD40.
ConclusionOur results show that MAPK3 can be used as a new prognostic biomarker to predict the prognosis of patients with CC.
Keywords: Autophagy, Bioinformatics, Uterine Cervical Neoplasms, Immune Infiltrates, Mitogen-activated protein - kinase 3} -
ObjectiveDysregulation of lipid and carbohydrate/fatty acid (FA) balance in Sertoli and germ cells alters the NADP+/NADPH ratio, resulting in metabolic autophagy in testicles. Tramadol (TRA) adversely affects spermatogenesisdevelopment, and it is not reversed within short periods of time after withdrawal. Therefore, the present study aimedto examine the boosting effect of different exercise training protocols (ETPs) on TRA-induced detrimental effects afterwithdrawal.Materials and MethodsIn this experimental study, 36 mature Wistar rats were separated into control and TRAsole(administered 40 mg/kg of TRA and euthanized 60 days after TRA administration), Con-TRA (stopped TRAadministration after 60 days, and continued for additional 60 days after withdrawal), TRA+low-intensity (TRA+LICT),TRA+ moderate-intensity (TRA+MICT), and TRA+high-intensity continuous (TRA+HICT) ETPs-induced groups (n=6/group, ETPs were initiated for 60 days after stopping TRA administration). Next, the intracytoplasmic carbohydrate andlipids/FAs content, testicular lactate and lactate dehydrogenase (LDH) levels, relative ratios of NADP+/NADPH, serumtestosterone levels, and the Leydig cells steroidogenic activity, the mRNA levels of Beclin-1, p62, LC3-I, and Atg7 aswell as the LC3-I/II+ germ and somatic cells mean distributions were analyzed.ResultsThe LICT and MICT could ameliorate the TRA-induced carbohydrates/lipids, FAs imbalance, increase lactate,LDH and testosterone levels, re-balance the NADP+/NADPH ratio, and reregulate the autophagy and steroidogenicactivities in the Leydig and Sertoli cells.ConclusionCollectively, LICT and MICT can ameliorate the TRA-induced metabolic-oxidative autophagy by rebalancingenergy survey in testicles and down-regulating autophagy reactions in Sertoli cells and rebalancing it in theLeydig cells.Keywords: Autophagy, Exercise Training, Metabolic Interactions, Spermatogenesis, Tramadol}
-
Objective (s)
Rhabdomyolysis (RM) is a serious fatal syndrome. The RM leads to acute kidney injury (AKI) as a fatal complication. The belief is that RM-induced AKI is triggered by myoglobin (MB). MB activates oxidative and apoptotic pathways. Trans-sodium crocetinate (TSC) is obtained from saffron. It has anti-oxidant and renoprotective effects. This research was designed to assess the mechanisms of MB-induced cytotoxicity in HEK-293 cells (human embryonic kidney cells) as well as the possible effects of TSC against MB-induced cytotoxicity.
Materials and MethodsHEK-293 cells were exposed to diverse concentrations of TSC (2.5, 5, 10, 20, 40, 80, and 100 µM) for 24 hr. Then, MB (9 mg/ml) was added to the cells. After 24 hr, cell viability was measured through MTT, and the values of ROS generation were calculated using DCFH-DA assay. Also, autophagy and apoptosis markers in cells were assessed by western blot analysis.
ResultsMB decreased viability and increased ROS levels in HEK-293 cells. However, pretreatment of HEK-293 cells with TSC for 24 hr reduced the cytotoxicity and ROS production caused by MB. Furthermore, MB enhanced both the apoptosis (cleaved caspase-3 and Bax/Bcl-2 ratio) and autophagy markers (LC3II/I ratio and Beclin-1) in HEK-293 cells. On the other hand, TSC pretreatment condensed the levels of autophagy and apoptosis criteria in response to MB cytotoxicity.
ConclusionTSC has a positive effect in preventing MB-induced cytotoxicity in HEK-293 cells by increasing anti-oxidant activity and regulation of apoptotic and autophagy signaling pathways.
Keywords: Apoptosis, Autophagy, Rabdomyolysis, Acute Kidney Injuries, Trans-sodium crocetinate, Myoglobin} -
مقدمه
ناباروری در واقع عدم باروری در زوجینی است که با وجود یک سال یا بیشتر تلاش برای تولید مثل، هیچ گونه لقاحی در آن ها رخ نداده است. مطالعه حاضر با هدف بررسی اثر 8 هفته تمرین شنا، سلول درمانی و مصرف ویتامین E بر تستوسترون و ژن های Lc31 و P62 بافت بیضه موش های مدل آزواسپرمی انجام شد.
روش کاردر این مطالعه تجربی، 40 سر رت 6 تا 8 هفته ای به صورت تصادفی انتخاب، و سپس مدل آزواسپرمی با داروی بوسولفان با دوز 40 میلی گرم القاء شد. پس از گذشت یک ماه موش ها در 8 گروه: 1) کنترل، 2) بیمار، 3) شم، 4) بیمار + تمرین، 5) بیمار + مکمل، 6) بیمار + سلول، 7) بیمار + مکمل + تمرین و 8) بیمار + سلول + تمرین، تقسیم شدند. سلول های بنیادی در ناحیه مجران دفران به میزان یک میلیون سلول برای هر موش پیوند زده شد، محلول خوراکی ویتامین E به میزان 100 میلی گرم بر کیلوگرم را به صورت گاواژ دریافت کردند و هم چنین گروه های تمرینی به مدت 8 هفته، 30 دقیقه در روز، 5 روز در هفته تمرین شنا را به صورت تداومی و با شدت ثابت 60 درصد ضربان قلب بیشینه انجام دادند. سطوح تستوسترون به روش الایزا و بررسی بیان ژن های P62 و LC31 بافت بیضه با تکنیک PCR Real Time انجام شد. تجزیه و تحلیل داده ها با استفاده از نرم افزار آماری SPSS (نسخه 26) انجام شد. میزان p کمتر از 05/0 معنی دار در نظر گرفته شد.
یافته هاالقای آزواسپرمی باعث کاهش معنی دار سطوح تستوسترون و بیان ژن های Lc31 و P62 بافت بیضه نسبت به گروه کنترل شد (05/0≥p)، اما در گروه های مکمل، سلول، تمرین، تمرین+ مکمل و تمرین+ سلول نسبت به گروه های بیمار و شم افزایش معنی دار را نشان دادند (05/0≥p).
نتیجه گیریدر مطالعه حاضر هم افزایی تمرین شنا با ویتامین E و سلول بنیادی مزانشیمی مشتق از مغز استخوان در بهبود شار اتوفاژی در رت های مدل تجربی آزواسپرمی مشاهده شد که ممکن است از این طریق در افزایش تستوسترون و یا حتی باروری موثر باشد.
کلید واژگان: آزواسپرمی, اتوفازی, تمرین شنا, سلول بنیادی مزانشیمی, ویتامین E}IntroductionInfertility is actually a lack of fertility in couples that has not conceived despite a year or more of trying to reproduce. The present study was performed with aim to investigate the effect of 8 weeks of swimming training, cell therapy and vitamin E consumption on testosterone and Lc31 and P62 genes in the testicular tissue of azoospermia model rats.
MethodsIn this experimental study, forty 6- to 8-week-old rats were randomly selected, and then the azoospermia model was induced with the busulfan at a dose of 40 mg. After one month, the rats were divided into 8 groups: 1) control, 2) patient, 3) sham, 4) patient + exercise, 5) patient + supplement, 6) patient + cell, 7) patient + supplement + exercise, and 8) patient + cell + exercise. Stem cells were transplanted in the vas deferens at the rate of one million cells for each mouse, they received an oral solution of vitamin E at the rate of 100 mg/kg by gavage, also the training groups performed swimming training continuously with a constant intensity of 60% of the maximum heart rate for 8 weeks, 30 minutes a day, 5 day of the week. Testosterone levels were measured by ELISA and the expression of P62 and LC31 genes in testicular tissue was measured by Real Time PCR technique. Data were analyzed using SPSS statistical software (version 26). P<0.05 was considered statistically significant.
ResultsInduction of azoospermia significantly decreased testosterone levels and the expression of Lc31 and P62 genes in testicular tissue compared to the control group (P≤0.05), but showed a significant increase in the supplement, cell, exercise, exercise+supplement and exercise+cell groups compared to the patient and sham groups (P≤0.05).
ConclusionIn the present study, the synergism of swimming exercise with vitamin E and mesenchymal stem cells derived from bone marrow in improving the autophagy flux in experimental rats with azoospermia was observed, which may be effective in increasing testosterone or even fertility.
Keywords: Azoospermia, Autophagy, Mesenchymal Stem Cell, Swimming Exercise, Vitamin E} -
Background
In the current study, the effects of cerium oxide nanoparticles (nanocerium; NC) on doxorubicin (DOX)-induced cardiomyopathy and its possible underlying mechanisms were addressed.
Methods32 adult male rats were allocated into 4 groups; i) control group, ii) NC group; rats received NC (0.2 mg/kg, i.p., daily), iii) DOX group; rats received DOX 4 mg/kg (2 injections with a 14-day interval), and iv) DOX+NC group as DOX but rats received NC. At the end of the experiment, ECG and ECHO recordings and assessments of the levels of cardiac enzymes (CK-MB, LDH), and myocardial oxidative stress (MDA, catalase, and GSH), the expression of LC3 and beclin1 (markers of autophagy), caspase3 (marker of apoptosis) by immunohistochemistry, the expression of acetyl-CoA carboxylase alpha (ACCA) by PCR, and 5’adenosine monophosphate-activated protein kinase (AMPK) levels in the heart tissues were performed.
ResultsThe DOX group displayed a prolonged corrected QT interval, an increase in cardiac enzymes (CK-MB and LDH), myocardial oxidative stress (high MDA with low catalase and GSH), expression of ACCA, caspase-3, beclin1, and LC3 in myocardial tissues, with reduction in myocardial AMPK levels, and myocardial contractility (low ejection fraction, and fractional shortening). On the other hand, administration of NC with DOX resulted in significant improvement of all studied parameters.
ConclusionsNC offers a cardioprotective effect against DOX-induced cardiomyopathy. This effect might be due to its antioxidant and antiapoptotic effects as well as to the modulation of autophagy and metabolic dysfunctions induced by DOX in the heart tissues.
Keywords: Autophagy, Cardiomyopathy, Cerium oxide nanoparticles, Doxorubicin, Echocardiography, Oxidative stress} -
Introduction
Diabetic neuropathy is a well-known complication of diabetes. Recently, hyperglycemia-induced toxicity has been confirmed to participates in multiple cellular pathways typical for neural deterioration. Nicotinamide phosphoribosyltransferase/pre-b cell colony-enhancing factor (Nampt/PBEF)/visfatin is a novel endogenous ligand that some studies have shown its neuroprotective effects on neurodegenerative disease. Therefore, we hypothesized that visfatin may prevent high glucose (HG)-induced neurotoxicity by inhibiting apoptosis, autophagy, and reactive oxygen species (ROS) responses properly.
MethodsIn this study, pheochromocytoma cell line 12 (PC12) cells were exposed to both HG concentrations (50, 75, 100, 125, 150 mM) and visfatin (50, 100, 150 ng/mL) at different time -points to determine the optimum time and dose of glucose and visfatin. To investigate the effects of visfatin on HG-induced damage in the PC12 diabetic neuropathy model, we examined ROS response, apoptosis, and autophagy using ROS detection kit, flow cytometry, and real-time PCR/Western blot, respectively.
ResultsWe determined that HG concentration significantly increased the ROS level and apoptosis of diabetic PC12 cells. However, visfatin treatment significantly decreased the ROS production (P<0.05) and apoptosis of diabetic PC12 cells (P<0.0001). Beclin-1 messenger ribonucleic acid (mRNA) level (P<0.05) and light chain 3 (Lc3)-II protein level (P<0.05) showed that the autophagy pathway is impaired by HG concentrations.
ConclusionWe concluded that visfatin can sufficiently decrease neural damage caused by ROS production and apoptosis under HG-induced toxicity.
Keywords: Visfatin, Diabetic neuropathy, Antioxidant, Apoptosis, Autophagy} -
Journal of Advances in Medical and Biomedical Research, Volume:31 Issue: 149, Nov-Dec 2023, PP 574 -584Background and Objective
Acute myeloid leukemia (AML) has a complex course of treatment, including chemotherapy and bone marrow transplantation, which mostly results in drug resistance and recurrence. Therefore, alternative therapies have attracted the attention of researchers. Mesenchymal stem cells exert their paracrine effects through the secretion of multiple cytokines and vesicles. Recent findings suggest the possible antitumor properties of MSCs by the secretion of micro-vesicles, and consequent activation of cell death pathways in cancer cells. The present study evaluated how micro-vesicles from human placental mesenchymal stem cells affect the autophagy and apoptosis pathways in AML.
Materials and MethodsAfter isolation and culture, hPMSCs were identified through flow cytometry. The Bradford method was employed to determine the concentration of MVs. The properties of MVs were confirmed by transmission electron microscopy (TEM) and DLS. Next, the KG1 cell line was exposed to MVs at concentrations of 25, 50, and 100 μg/ml for 24 hours. Subsequently, apoptosis was assessed using an Annexin V-FITC/PI kit, and ROS activity was gauged through the utilization of H2DCFDA. The gene expression in the autophagy and apoptosis pathways was investigated by using the real-time PCR technique.
ResultsAfter 24 hours of treatment, a rise in intracellular ROS accumulation and apoptosis was observed in all groups compared to the control group. The mean intracellular ROS accumulation at the concentrations of 25, 50, and 100 μg / ml of the samples and the control group was 62.21% (P<0.0002), 66.25% (P<0.0001), 62.55% (P<0.0001), and 26.1% (P<0.0001), respectively. The apoptosis indices at the concentrations of 25, 50, and 100 μg / ml of the samples were 62.6% (P<0.0002), 46.0% (P<0.0001), and 48.2% (P<0.0001), respectively. Furthermore, analyzing genes through RT-PCR indicated a considerable increase in the expression of autophagy-related and pro-apoptotic genes.
ConclusionOur findings indicate that hPMSC-MVs induce Cell death pathways of autophagy and apoptosis in the KG1 cell lines. Additionally, hPMSC-MVs exhibited heightened impactful anti-proliferative and pro-apoptotic outcomes on KG1 cells in vitro.
Keywords: Placental Mesenchymal Stem Cell, Micro-vesicles, Acute Myeloid Leukemia, Autophagy, Apoptosis} -
Objective
The aim of this study was to synthesize chitosan nanoparticles (Cs NPs) for resveratrol (RSV) delivery and assess their effectiveness in inducing autophagy in MDA-MB 231 cells.
Materials and MethodsIn this experimental study, Pure and RSV-loaded Cs NPs (RSV. Cs NPs) were prepared via the ionic gelation method, and their physicochemical properties were characterized using standard techniques, and RSV release was measured in vitro. MDA-MB 231 cells were incubated with RSV, Cs NPs, and RSV. Cs NPs and Half-maximal inhibitory concentration (IC50) values were calculated following the MTT test. Cell viability was assessed by lactate dehydrogenase (LDH) assay, and autophagy was evaluated using the real-time polymerase chain reaction (PCR).
ResultsNP formation was confirmed with the analysis of FTIR spectra. Pure and RSV. Cs NPs had 36.7 and 94.07 nm sizes with 18.3 and 27 mV zeta potentials, respectively. Above 60% of RSV entrapped within NPs was released in an initial burst manner followed by a gradual release till 72 hours. Cs and RSV. Cs NPs restrained cell proliferation at lower concentrations. RSV. Cs NPs showed the highest anticancer effect and stimulated autophagy, indicated by increased Beclin-1 ATG5, ATG7, LC3A, and P62 expression.
ConclusionRSV. Cs NPs show promising effects in inhibiting invasive breast cancer (BC) cells in vitro by inducing autophagy.
Keywords: Antineoplastic Effects, Autophagy, Breast Neoplasm, Resveratrol} -
مقدمه و هدف
کاهش حجم عضلانی یک عامل مهم برای کاهش عملکردهای بدن در پیری می باشد. مسیرهای سلولی پیچیده مانند اتوفاژی به شدت به سلامت مرتبط است و ارتباط پیچیده ای بین اتوفاژی و پیری وجود دارد؛ بنابراین هدف از انجام تحقیق حاضر تاثیر تمرین مقاومتی بر محتوای پروتیین های اتوفاژی Beclin1 و Ambra1 در عضله بازکننده طویل انگشتان پا (EDL) موش های صحرایی سالمند بود.
مواد و روش هاپژوهش حاضر از نوع تجربی-بنیادی است که 12 سر موش صحرایی نر 20 ماهه از نژاد اسپراگ داولی با میانگین وزنی 30±400 گرم به صورت تصادفی به 2 گروه: 1. کنترل (6 سر) و 2. تمرین مقاومتی (6 سر) تقسیم شدند. برنامه تمرین مقاومتی شامل صعود از نردبان مخصوص جوندگان به مدت 8 هفته، هفته ای 3 جلسه بود. آزمودنی ها از یک نردبان عمودی با شیب 85 درجه به طول یک متر با 26 پله و دو سانتی متر فضای بین هر پله بالا می رفتند. بعد از 48 ساعت پس از آخرین جلسه تمرین EDL از بدن موش های صحرایی برداشته شد. تجزیه و تحلیل داده ها از طریق آزمون t-مستقل در نرم افزار گراف پد پریسم نسخه 5/9 انجام شد. سطح معنی داری P≤0.05 بود.
نتایجهشت هفته تمرین مقاومتی منجر به کاهش میزان پروتیین Beclin1 (0001/0=P) و Ambra1 (0212/0=P) در عضله EDL موش های صحرایی پیر شد.
نتیجه گیریکاهش محتوای درون سلولی این عوامل از طریق انجام تمرین مقاومتی می تواند از اتوفاژی سلول های عضلانی آزمودنی های سالمند جلوگیری کند و این به معنای آتروفی کمتر است.
کلید واژگان: پیری, اتوفاژی, پروتئین آمبرا-1, پروتئین بکلین-1, تمرین مقاومتی}Background and ObjectiveDecreased muscle mass is an important factor in the reduction of body function in old age. Complex cellular pathways such as autophagy are strongly related to health and there is a complex relationship between autophagy and aging; therefore, the aim of this study was to investigate the effect of resistance training on the levels of autophagy proteins Beclin1 and Ambra1 in the Extensor Digitorum Longus (EDL) muscle of elderly rats.
Materials and MethodsThe current research was of an experimental-fundamental type, in which 12, 20-month-old male Sprague-Dawley rats with an average weight of 400 ± 30 g were randomly divided into two groups: 1) control (6 heads) and 2) resistance training (6 heads). The resistance training program included climbing the rodent ladder for eight weeks, three sessions per week. The subjects climbed a vertical ladder with an 85-degree incline, one meter long, 26 rungs and two cm of space between each rung. After 48 hours after the last training session, EDL muscle tissue was removed. Data were analysed using an independent t-test in the GraphPad Prism version 9.5 software. The significance level was set at P < 0.05.
ResultsEight weeks of resistance training led to decreased Beclin1 (P=0.0001) and Ambra1 (P=0.0212) protein levels in the EDL muscle of old rats.
ConclusionReducing the intracellular content of these factors through resistance training can prevent autophagy in the muscle cells of elderly subjects, resulting in less atrophy
Keywords: Aging, Autophagy, Ambra1, Beclin1, Resistance training} -
Despite antiviral treatment, some patients with chronic hepatitis B (CHB) progress to cirrhosis. Enhancement of autophagy was implicated in the proliferation of hepatitis B in hepatocytes. This study aimed to evaluate the potential role of autophagy in the progression of liver fibrosis in patients receiving antiviral treatments and having completely inhibited viral replication. This descriptive-analytical study was designed and conducted in 2020 at Mottahhari Hepatitis Clinic affiliated with Shiraz University of Medical Science (Shiraz, Iran). Patients who were on anti-hepatitis B nucleotide treatments for at least two years, and those who were not cirrhotic at baseline but later progressed to cirrhosis were identified to be included in the case group. Besides, for the control group, patients on the nucleotide regimens who did not have cirrhosis at baseline or during follow-up were randomly selected. Ultimately, 16 cases and 14 controls were included in the study. Data were analyzed using SPSS software, and P<0.05 was considered statistically significant. Serum Beclin-1 and LC3 levels were compared between the two groups using enzyme-linked immunosorbent assays. The t test was used to assess the statistical differences between the case and control groups. Beclin-1 level was significantly higher in cirrhosis patients than the control group (1283±244 vs. 1063±257, P=0.024). However, there was no statistical difference between the level of LC3 in the cirrhotic group (168±31) and the control group (150±16) (P=0.065). Autophagy may have a role in the progression of cirrhosis in patients with CHB. Future larger prospective studies are required to determine the effect of blocking on the progression of liver disease in this population.
Keywords: Autophagy, Hepatitis B, chronic, fibrosis, Beclin-1} -
Objective(s)Dexmedetomidine (Dex) is a potent α2-adrenergic receptor(α2-AR) agonist that has been shown to protect against sepsis-induced lung injury, however, the underlying mechanisms of this protection are not fully understood. Autophagy and the Smad2/3 signaling pathway play important roles in sepsis-induced lung injury, but the relationship between Dex and Smad2/3 is not clear. This study aimed to investigate the role of autophagy and the Smad2/3 signaling pathway in Dex-mediated treatment of sepsis-induced lung injury. Sepsis was performed using cecal ligation and puncture (CLP) in C57BL/6J mice.Materials and MethodsMice were randomly assigned to four groups (n=6 per group): sham, CLP, CLP-Dex, and CLP-Dex-YOH, Yohimbine hydrochloride (YOH) is an α2-AR blocker. The cecum was carefully separated to avoid blood vessel damage and was identified and punctured twice with an 18-gauge needle. The pathological changes, inflammatory factor levels, oxidative stress, autophagy, Smad2/3 signaling pathway-related protein levels in lung tissues, and the activity of superoxide dismutase (SOD) and malonaldehyde (MDA) in the serum were measured.ResultsCLP-induced lung injury was reflected by increased levels of inflammatory cytokines, apoptosis, and oxidative stress, along with an increase in the expression of autophagy and Smad2/3 signaling pathway-related proteins. Dex could reverse these changes and confer a protective effect on the lung during sepsis. However, the administration of YOH significantly reduced the positive effects of Dex in mice with sepsis.ConclusionDex exerts its beneficial effects against sepsis-induced lung injury through the regulation of autophagy and the Smad2/3 signaling pathway.Keywords: Acute lung injury, Autophagy, Dexmedetomidine, Sepsis, Smad2, 3}
-
Objective (s)
5-Fluorouracil (5-FU) is currently the main drug used in chemotherapy for gastric cancer (GC). The main clinical problems of 5-FU therapy are insensitivity and acquired resistance to 5-FU. The mechanism of GC cell resistance to 5-FU is currently unknown.
Materials and MethodsThis study employed next-generation sequencing (NGS) to analyze the differentially expressed genes (DEGs) in chemotherapy-sensitive and non-sensitive GC tissues. In addition, a bioinformatics analysis was conducted using the GC dataset of GEO, and further validated and explored through in vitro experiments.
ResultsThyroid adenoma-associated gene (THADA) was highly expressed in GC tissues from chemotherapy-sensitive patients and was an independent prognostic factor in GC patients receiving postoperative 5-FU adjuvant chemotherapy. Notably, heightened THADA expression in GC cells was associated with the down-regulation of autophagy-related proteins (LC-3, ATG13, ULK1, and TFEB). Furthermore, the PI3K/AKT/mTOR signaling pathway and mTORC1 signaling pathway were remarkably increased in patients with elevated THADA expression. THADA expression was associated with mTOR, the core protein of the mTOR signaling pathway, and related proteins involved in regulating the mTORC1 signaling pathway (mLST8, RHEB, and TSC2). THADA exhibited inhibitory effects on autophagy and augmented the sensitivity of GC cells to 5-FU through the PI3K/AKT/mTOR signaling pathway.
ConclusionThe findings suggest that THADA may be involved in the regulatory mechanism of GC cell sensitivity to 5-FU. Consequently, the detection of THADA in tumor tissues may bring clinical benefits, specifically for 5-FU-related chemotherapy administered to GC patients with elevated THADA expression.
Keywords: Autophagy, Fluorouracil, Human, Stomach Neoplasms THADA protein, TOR Serine-Threonine- Kinases} -
Objective (s)
The primary gene mutations associated with nasopharyngeal carcinoma (NPC) are located within the phosphoinositide 3-kinase-mammalian target of rapamycin signaling pathways, which have inhibitory effects on autophagy. Compounds that target autophagy could potentially be used to treat NPC. However, autophagy-related molecular targets in NPC remain to be elucidated. We aimed to examine levels of autophagy-related genes, including autophagy-related 4B cysteine peptidase (ATG4B) and gamma-aminobutyric acid (GABA) type A receptor-associated protein-like 1 (GABARAPL1), in NPC cells and explored their potential role as novel targets for the treatment of NPC.
Materials and MethodsThe mRNA and protein expression of autophagy-related genes were detected in several NPC cells. Levels of GABARAPL1 were modified by either overexpression or knockdown, followed by examining downstream targets using RT-qPCR and western blotting. The role of GABARAPL1 in NPC proliferation and apoptosis was examined by flow cytometry. Furthermore, the role of GABARAPL1 was assessed in vivo using a nude mouse xenograft tumor model. The underlying mechanism by which GABARAPL1 regulated nasopharyngeal tumor growth was investigated.
ResultsAutophagy-related 4B cysteine peptidase (ATG4B), GABARAPL1, and Unc-51-like kinase 1 (ULK1) were significantly down-regulated in multiple NPC cell lines. Overexpression of GABARAPL1 up-regulated the expression of autophagy-related proteins, decreased the level of hypoxia-inducible factor (HIF)-2α, and induced apoptosis in NPC cells. Importantly, overexpression of GABARAPL1 slowed tumor growth. Western blotting showed that autophagy was activated, and HIF-2α was down-regulated in tumor tissues.
ConclusionHIF-2α, as a substrate for autophagic degradation, may play an interesting role during NPC progression.
Keywords: ATG4B, Autophagy, GABARAPL1, Hypoxia inducible factor, Nasopharyngeal carcinoma}
- نتایج بر اساس تاریخ انتشار مرتب شدهاند.
- کلیدواژه مورد نظر شما تنها در فیلد کلیدواژگان مقالات جستجو شدهاست. به منظور حذف نتایج غیر مرتبط، جستجو تنها در مقالات مجلاتی انجام شده که با مجله ماخذ هم موضوع هستند.
- در صورتی که میخواهید جستجو را در همه موضوعات و با شرایط دیگر تکرار کنید به صفحه جستجوی پیشرفته مجلات مراجعه کنید.