اتوفاژی

Autophagy is responsible for maintaining cellular homeostasis by degrading and recycling macromolecules and unwanted intracellular components, such as damaged organelles. Trans-chalcone is a compound with anti-cancer and anti-inflammatory properties. However, its impact on autophagy in lung tissue has not been investigated yet. Therefore, this study evaluated the effects of trans-chalcone on autophagy-related Gene Expressions in the lung.

Twelve male rats were randomly divided into control and chalcone groups. In the control group, rats were orally gavaged with Tween 80(10%), while in the chalcone group, rats were orally gavaged with trans-chalcone once a day for six weeks. Blood and lung samples were collected from overnight fasted rats. Serum insulin and glucose levels were used to estimate the fasting glucose-to-insulin ratio. Further, a real-time polymerase chain reaction was performed to assess the levels of p62, LC3, and Beclin-1 gene expression in the lungs of rats.

 Trans-chalcone significantly increased the fasting glucose-to-insulin ratio (insulin sensitivity). In addition, this compound significantly increased Beclin-1 mRNA expression levels and decreased p62 expression levels in the lungs of rats. Nevertheless, the upregulatory effect of this compound on LC3 expression was not statistically significant.

Based on the findings, trans-chalcone increases insulin sensitivity and has a regulatory effect on autophagy in the lungs of healthy rats. Changes in Beclin-1 and p62 mRNA levels reflect this issue.

The ability of trans-chalcone to up-regulate Beclin-1, a key marker of autophagy, and down-regulate p62 mRNA expression indicates its regulatory effect on autophagy. Further studies are required to validate the potential of this chalcone as a promising treatment for autophagy-related lung diseases.

In people with diabetes, metabolic changes can affect the body's response to physical activity. On the other hand, for people with diabetes, exercise can be a powerful tool to manage diabetes and improve overall health through key regulatory proteins such as adenosine monophosphate-activated protein kinase (AMPKα1/2), dynamin-like protein (DLP1), and autophagy-related protein 13 (ATG13). In diabetes, AMPK regulation is often disrupted, contributing to the metabolic imbalances that characterize diabetes. In diabetes, disruption of DLP1 protein as a key regulator of mitochondrial fission leads to the accumulation of damaged mitochondria and metabolic imbalance. ATG13, as an autophagy regulator causes the recycling of damaged cells and damaged components.

This study was conducted in May to July 2023. In this experimental research, 12 two-month-old male Sprague-Dawley rats with an average weight of 280±30 grams participated. To induce type two diabetes, nicotinamide solution with a dose of 110 mg/kg and streptozotocin (STZ) with a dose of 60 mg/kg were injected, and blood glucose between 126 and 260 mg/dl was determined as the index of diabetes induction. Then the diabetic rats were randomly divided into training (six heads) and control groups (six heads). The moderate-intensity interval training (MIIT) group trained for 4 weeks and four sessions every week. The MIIT program consisted of 4 rounds of 3 minutes with an intensity equal to 55-75% of the maximum speed and active rest periods of two minutes with an intensity of 35-45% of the maximum speed. After 24 hours from the last training, the rats were anesthetized and the soleus muscle tissue was isolated and the proteins were measured by western blot methods.

The results showed that MIIT causes a non-significant increase in AMPK protein (P=0.29) and ATG13 (P=0.079), while it has a significant decrease in DLP1 (P=0.002).

It seems that MIIT, through decreasing DLP1, can have a beneficial effect on energy metabolism and autophagy process in order to optimize cells mitochondria in the soleus muscle of diabetic rats.

Autophagy is a fundamental process in eukaryotic cells, essential for maintaining cellular homeostasis and promoting survival. This process involves the formation of a structure known as the autophagosome, which sequesters damaged cellular components such as misfolded proteins and dysfunctional organelles. These components are subsequently transported to lysosomes for degradation. Autophagy allows cells to withstand various stress conditions, including nutrient deprivation, hypoxia, and microbial infections. There are three primary types of autophagy: macroautophagy, microautophagy, and chaperone-mediated autophagy, each characterized by distinct mechanisms and features. The autophagy process is tightly regulated by autophagy-related genes (ATG) and consists of several stages: induction, autophagosome formation, fusion with lysosomes, and cargo degradation. Dysfunctional autophagy has been implicated in the development of various diseases, including cancer, neurodegenerative disorders, metabolic diseases, and bacterial or viral infections. Recent studies have highlighted the dual role of autophagy in cancer: while it can act as a tumor suppressor in early stages, it may also support tumor cell survival in advanced stages. In the nervous system, autophagy helps prevent the accumulation of harmful proteins and supports neuronal function. Additionally, autophagy plays a significant role in combating invasive pathogens, serving as a defensive mechanism against bacteria and viruses. Research indicates that autophagy is a promising target for developing new therapeutic strategies for a wide range of diseases. In-depth investigations into the molecular pathways regulating autophagy, particularly the mTOR and AMPK pathways, offer potential avenues for innovative treatments. This review provides a comprehensive analysis of the mechanisms and functions of autophagy, exploring its association with various human diseases. It presents a novel perspective on the potential clinical applications of autophagy, highlighting its role in the development of therapeutic strategies and deepening our understanding of this essential cellular process.

Despite the protective effect of ischemic preconditioning (IPC) from tissues, its effect on diabetes-induced excessive autophagy is not clear. Autophagy could be inhibited or activated through exercise. The present study aimed to investigate the effect of endurance training and remote IPC on myocardial Beclin-1 gene expression in diabetic rats.

In this experimental research, 35 Wistar rats were randomly divided into seven groups: normal control (C), diabetic (D), diabetic one leg ischemia (OI), diabetic two legs ischemia (TI), diabetic endurance training (E), diabetes one leg ischemia + endurance training (OIE), diabetes two legs ischemia+ endurance training (TIE). IPC was included three 5-minute cycles of ischemia, followed by five minutes of reperfusion. The endurance training groups performed exercise training for six weeks and five days a week and was included running on a treadmill. The speed for the first week is set at 9 meters per minute for 15 minutes. By the sixth week, the training speed was increased to 18 meters per minute for 30 minutes. Beclin-1 gene expression was measured by RT-PCR. Data were analyzed by one-way analysis of variance and Tukey post hoc tests.

Beclin-1 gene expression significantly increased in D group compared to C group (p=0.0001). Becli-1 gene expression significantly decreased in OI (p=0.0001), TI (p=0.0001), E (p=0.0001), OIE (p=0.0001) and TIE (p=0.0001) compared to the D.

It seems that the effect of ischemia preconditioning in decreasing Beclin-1 is independent of the ischemia-affected muscle mass. Endurance training with IPC is more effective in decreasing Beclin-1 in diabetes than any of the exercise and IPC interventions alone.

Defective lipophagy is associated with metabolic disorders. This study investigated the effect of four weeks of aerobic exercise in a fasted state on hepatic unc-51 like autophagy activating kinase 1 (ULK1) in male rats with non-alcoholic fatty liver disease (NAFLD). In this experimental research, 30 male Wistar rats with an NAFLD model were randomly divided into control groups: fasting, 3-day training, 5-day training, fasting + 3-day training, and fasting + 5-day training. Unlike other rats that had 24-hour access to food, the fasting groups received the same amount of nutrition during 10 hours. Continuous running was done for four weeks with 3 and 5 sessions per week and in two conditions of feeding and fasting. Statistical analysis was done with SPSS software Version 26 using one-way variance analysis and Bonferroni test with a significance level of (P≤0.05). A significant increase in the expression of the ULK1 gene was observed in the fasting, fasting + 3-day training, and fasting + 5-day training groups compared to the control and 3-day training groups (P<0.05). The increase of ULK1 in the fasting group was higher than in the 3-day- and 5-day training groups (P<0.05). Also, the increase of ULK1 in the fasting + 3-day training and fasting + 5-day training groups was significantly higher than the 5-day training group (P<0.05). Fasting and exercise in the fasting state increase lipophagy and might improve NAFLD.

Decreased 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.

The 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.

Eight 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.

Reducing the intracellular content of these factors through resistance training can prevent autophagy in the muscle cells of elderly subjects, resulting in less atrophy

Background and Objectives In recent years, flavonoids such as quercetin have been considered as newanticancer drugs. The mechanisms of action of quercetin include cell cycle arrest, inhabitation of cellproliferation, and induction of apoptosis. This study aims to reduce quercetin’s side effects by increasingMCF-7 breast cancer cells’ sensitivity to this drug and facilitating the cytotoxic effects of quercetin atlower concentrations.Subjects and Methods In this study, the MTT assay was used to determine the concentration that reducedthe cell viability by 50% (i.e. lethal concentration 50 or LC50). Then, the expression of the DNAfragmentation factor-45 (DFF45) and some genes in the apoptosis pathway (caspase3, p53, BAX, BCL-2,AIF), the autophagy pathway (LC3, ATG5, Beclin, DRAM) and the AKT/mTOR pathway (AKT1, mTOR, andPTEN), in cells treated with siRNA, quercetin, and quercetin+siRNA using the real-time PCR.Results According to the results of MTT assay, the LC50 value for quercetin was determined 220 μM.The results indicated the initiation of cell death through autophagy pathways. The combined treatment(quercetin+siRNA) increased the mechanism of cancer cell death more than the quercetin treatmentalone.Conclusion One of the regulating pathways of apoptosis is forcing the inhibitory effect of DFF45 onDFF40/CAD nuclease. Down regulation of DFF45, along with quercetin administration, can lead to inductionof breast cancer cell death which can be a novel technique for the treatment of breast cancer.

Infertility in men is 10-20% of cases due to azoospermia and usually due to disorders of the reproductive system. Normally, the population of men with azoospermia is estimated to be around 2% (1) and it has been shown that in 20% of infertile men, azoospermia is the main cause of infertility (2). Non-obstructive azoospermia is a state in which no sperm is observed in ejaculation and is related to intra-testicular disorders and as a result spermatogenesis disorders, while in obstructive azoospermia, spermatogenesis is normal and the defect is related to obstruction in the ejaculatory ducts (3). In a study, decreased expression of autophagy pathway genes (Lc3B, Beclin1) was observed in patients with azoospermia (4). The aim of this study was to investigate the effect of swimming, cell and laser training on the expression of genes involved in autophagy in azoospermia model mice.

The samples of the present study were male Wistar laboratory rats, which were under control in the laboratory in terms of many variables, therefore, the present study was of an experimental type. 30 6 to 8 week old rats from the research center and Reproduction of laboratory animals in Tehran were randomly selected. In order to create azoospermia model, the drug busulfan was injected intraperitoneally for each rat at a dose of 40 mg/kg of body weight (15). After a month of inducing the model, the rats in each group were divided as follows: Patient control group (one month after creating the model until the end of the study, they remained for 8 weeks), healthy control group (kept for 8 weeks), patient control group + low power laser (one month after creating the model, low laser Power with a wavelength of 632.8 nm and a power of 10 mW and an energy of 3 joules was applied three times in the entire study period with an interval of one week in the testicular region of azoospermic rats and rats until the end of the study for 8 weeks. were maintained), the patient control group + exercise (one month after creating azoospermic mice for 8 weeks, they swam daily for 30 minutes a day, 5 days a week), the patient control group + cell (one month later From the creation of azoospermic mice, stem cells were transplanted in the vas deferens region at the rate of one million cells per mouse in the right testis and the rats were kept for 8 weeks until the end of the study), patient control group + cells + low laser power + exercise (one month after the creation of azoospermic mice, stem cells were transplanted once in the vas deferens in the amount of one million cells for each mouse, then after a week of low power laser cell transplantation with wavelength 632.8 nm and power of 10 mW and energy of 3 joules were applied three times during the entire study period with an interval of one week and after the healing of the wound of the cell graft area on the abdomen, it was applied topically for 30 minutes a day. They swam 5 days a week, which lasted for 8 weeks). Tissue sampling was done from the testicular tissue of mice under completely similar conditions and in basic conditions (two days after the end of the training period). In order to eliminate the acute effect of training, sampling of the animals was done 48 hours after the last swimming training program. For this purpose, the animals were anesthetized by peritoneal injection of ketamine (30-50 mg/kg) and xylazine (5-3 mg/kg) and then killed, and after killing the transplanted tissues, they were evaluated for genetic studies. To check the expression of the studied genes in each group, real time PCR technique was used to examine the tissues. First, primer design was done and then total RNA was extracted from the tissues and converted into cDNA. Then, the cDNA was amplified by PCR and analyzed for the expression of the mentioned genes. To analyze the findings of this research, Smirnov's Kalmograph tests, one-way analysis of variance and Tukey's were used to compare between different groups. All calculations were done using SPSS/22 statistical software and at a significant level of P≤0.05.

The results showed that there is a significant difference between the average expression of the Beclin gene in testicular tissue in different research groups; The control group has a significant difference with the model group at the confidence level of 0.01, and the model group has a significant difference with the cell, laser and training group at the confidence level of 0.05. Also, the results show that cells, laser and exercise simultaneously had an effect on the expression of Beclin gene in testicular tissue in azoospermia model mice. Also, the next finding showed that there is a significant difference between the average LC3 gene expression of testicular tissue in different research groups; The control group has a significant difference with the model group at the confidence level of 0.01, and the model group has a significant difference with the cell, laser and training group at the confidence level of 0.05. Also, the results show that cells, laser and training simultaneously had an effect on the expression of LC3 gene in testicular tissue in azoospermia model mice.

The results of the research showed that by inducing the azoospermia model, the expression of LC3 and Beclin-1 genes in the testicular tissue of mice increased significantly compared to the control group. On the other hand, with the implementation of exercise, cell and laser treatment methods, the expression of the mentioned genes in mice decreased compared to the azoospermic group, showing that this decrease was significant only in the combined exercise, cell and laser group. Research has shown that exercise can be a key factor in the regulation of proteins involved in the autophagy pathway, and the regulation of autophagy by exercise can be a key process in cellular and molecular mechanisms (11,10). The main path of the proteins involved in the autophagy process is regulated by complex regulatory mechanisms, which can be different input signals such as nutrients, growth factors, hormones, intracellular calcium concentration, ATP level, hypoxia, etc. The main regulatory pathway of these factors is the mTORC1 pathway, which is activated in cellular responses such as growth, proliferation, protein synthesis, and autophagy (11). The mTORC1 pathway can activate or inhibit the autophagy mechanism by regulating ULK1, ATG13 and FIP200 proteins (25). Various studies have shown that LC3 can increase cell death or its survival (26), it is also known as one of the effective factors in autophagy, which according to the available evidence can have an apoptotic function (27). It has been reported that decreased autophagic activity due to decreased expression of LC3 and Beclin-1 can be associated with tumorigenesis and increased tumor growth (28). No research was found that investigated the effect of stem cells and laser therapy on the expression of genes involved in autophagy. The results of the present study showed that cell therapy and laser therapy alone and in combination do not have a significant effect on the expression of LC3 and Beclin-1 genes in the testicular tissue of azoospermia model mice, but cell therapy and laser therapy in combination with exercise caused a significant decrease in these genes. And somehow it inhibited autophagy in testicular tissue of azoospermia model mice. Therefore, it is possible that exercise combined with cell therapy and laser therapy by inhibiting autophagy in the testicular tissue of azoospermia model mice induced with busulfan exerts its protective effect and in this way causes the fertility of azoospermia model mice, but a definite opinion needs more research in this regard. It is the context. In general, it has been shown in the research that autophagy is activated in pathological conditions and may have destructive effects on the tissue. In the present study, the induction of the azoospermia model by busulfan leads to an increase in the genes involved in autophagy and in some way activates the pathway that exercise Exercise in combination with cells and laser therapy by reducing genes and somehow inhibiting autophagy may exert its protective effect and thus prevent infertility in mice.

Cardiac ischemia is the major cause of morbidity and mortality which can be increased by Statins. This study aimed to increase the effectiveness of simvastatin in the form of niosomes.

In this study, 25 male Wistar rats were divided into 5 groups: control, ischemia (induced by closed LAD), ischemia receiving nano-niosomes, ischemia receiving simvastatin, and ischemia receiving simvastatin-loaded nano-niosomes. One month after the drug injection, RNA was extracted from the heart tissue of the studied groups, cDNA was synthesized, and a real-time PCR test was performed using specific primers. SPSS 21.0 software was used for statistical analysis. Analysis of variance was used to investigate the effect of the interventions, and Tukey's post hoc test was used to investigate a significant difference (P<0.05) between the control groups and other groups as well as between intervention groups.

Apoptosis and autophagy increased significantly in the ischemia group compared to the control group (P<0.05). In the simvastatin-loaded nano-niosomes group, compared to the simvastatin group, apoptosis and autophagy showed a significant decrease (P<0.05), and also in both simvastatin-loaded nano-niosomes and simvastatin group, compared to the control group, apoptosis and autophagy showed a significant decrease. (P<0.05).

Simvastatin is an effective drug in the recovery of cardiac ischemia, but the main problem in using simvastatin is its instability and degradability, and the use of its niosomes form solves this problem properly.

Simvastatin‑loaded nano‑niosomes is more effective in reducing heart ischemia damage compared to simvastatin.

Aging indicates physiological and biological changes in humans that are associated with a decrease in physical strength and cause changes in the anatomy and physiology of the body. It has been reported that at a rate of one percent per year, muscle mass decreases from the age of 30 to 60 and increases from the age of 60 onwards. The incidence of diseases such as type 2 diabetes, metabolic syndrome and cardiovascular disease, as well as chronic diseases of the musculoskeletal system and cancer are increasing, all of which can be affected by a decrease in muscle mass (1).Autophagic activity has been shown to decrease with age and may contribute to the accumulation of damaged macromolecules and organs during aging. Failure in the autophagy process exacerbates age-related diseases such as nerve damage or cancer (5). p62, a classical autophagy receptor, is a multifunctional protein located throughout the cell and involved in many signal transduction pathways, including the Keap1-Nrf2 pathway (7). p62 is an autophagy substrate used to report autophagic activity. Recently, p62 has been shown to deliver ubiquitinated proteins, including tau, to the proteasome for degradation. In addition, it can be a shuttle between the nucleus and the cytoplasm to facilitate and control the quality of cytosolic proteins (6).It has been well established that regular exercise improves physical function and brings important health benefits that inhibit many pathological diseases such as cancer as well as cardiovascular, metabolic and neurodegenerative diseases (8). Exercise promotes phenotypic adaptation in skeletal muscle, which includes mitochondrial biogenesis, angiogenesis, fiber deformation, and improved insulin sensitivity (9, 10). Regarding the effect of exercise on changes in autophagy, it has been reported that aerobic and resistance training leads to changes in autophagy indices (11, 12). Atroastetin is a type of statin that has a reducing effect on cholesterol production, as well as antioxidant, anti-inflammatory, anti-apoptotic and tissue protective effects in some pathological conditions (15-17). Study of mechanisms affecting the process of autophagy following exercise, including continuous and intermittent exercise with atroastetin supplementation can improve this process (22). Therefore, the aim of this study was to investigate the effect of eight continuous and interval exercises with atroastetin supplementation on mRNA p62 expression in elderly rats with type 2 diabetes.

This is a semi-experimental study. 63 old male Wistar rats (mean weight 300 to 350 g) categorized into eight groups that included; 1) healthy control group, 2) diabetic control group, 3) diabetic group + continuous exercise, 4) diabetic group + interval exercise, 5) diabetic group + supplement, 6) diabetic group + continuous exercise + supplement, 7) diabetic group + interval exercise + supplement, and 8) saline group. Diabetes was induced by injection of 50 mg/kg streptozotocin. continuous and interval exercise program was performed, which included running at a speed of 15 to 29 meters per minute for 5 to 22 minutes for continuous aerobic exercise and six 2.5-minute sets with four minutes of rest between each set for interval exercise. Atherostatin supplementation with dose of 20 mg per kg body weight was injected intraperitoneally daily. One-way ANOVA was used for comparison between groups at the p <0.05.

The results showed that P62 mRNA expression was significantly reduced in all groups compared to the healthy and diabetic control group (p<0.001), but there was no significant difference between the other groups (p<0.05). (fig. 1).

The results of the present study showed that despite the decrease in P62 mRNA expression in the experimental groups compared to the control and patient groups, no significant difference was observed between the other experimental groups. It seems that taking atroastetin supplementation, despite its anti-inflammatory and anti-oxidant effect, has no effect on the process of autophagy, which can be due to the amount used during the training period or the short-term use of atherostatin. Exercise has been reported to induce autophagy in skeletal muscle. Key autophagy proteins, including p62 and LC3-II, change significantly after exercise. These changes are consistent with an increase in autophagy after exercise. Tarawan et al. (2019) reported that exercise significantly reduced P62 in the muscles, which is more pronounced at moderate intensities. The researchers argued that at moderate intensities relative to high and low intensities, autophagic activity decreased after exercise and recommended moderate-intensity exercise (25). Exercise by phosphorylating Akt can inactivate the autophagy pathway through the PI3K-Akt-MTOR mediated pathway. Due to its unique properties, muscle fibers seem to play a significant role in the activity of autophagy and proteins involved in this process (26). Mejías et al. In the study showed that eight weeks of aerobic and resistance training in elderly men and women significantly increased LC3II / I, Atg16-12 and Bcl-2, but p62 expression decreased significantly (11, 12). Therefore, it is thought that exercise play a decisive role in inhibiting autophagy. Jamart et al. (2013) concluded that low-intensity exercise after fasting increases the activity of autophagy in skeletal muscle, which is due to a decrease in Akt pathway activity compared to satiety (27). The results of the present study showed that compared to the control and disease groups, P62 mRNA expression was significantly reduced; However, this decrease was not significant between the training groups and the training groups with supplementation. These results appear to be influenced by research methodology that the duration of the training period was insufficient or that the dose of atroastetin was low. continuous and interval exercise with atroastetin supplementation with anti-inflammatory and anti-oxidant effects on muscle cells is thought to reduce autophagy activity, resulting in a significant decrease in P62 mRNA expression compared with the patient group. In fact, exercise reduces the onset of autophagy in the skeletal muscle of diabetic rats by improving the antioxidant system and reducing the release of cytochrome c. However, the amount of reactive oxygen species has been reported to be high in animal and human species with type 2 diabetes (28). Therefore, continuous and interval exercise with atroastetin supplementation has been able to reduce autophagy markers, including P62 mRNA. There were some limitations in the present study, such as the lack of measurement of other autophagic indices such as LC3-II. It can also be noted that PI3K-Akt-MTOR autophagy pathway indices are not measured. Therefore, a study measuring these indicators in elderly samples with type 2 diabetes is recommended. According to the results, it seems that continuous and interval exercise with atherostatin supplementation can reduce P62 mRNA in elderly type 2 diabetic rats.

One of the major problems in old age is sarcopenia, which can be prevented by doing various exercise training. The purpose of the study was to investigate the effect of resistance and endurance training on the expression of genetic factors involved in muscle autophagy in elderly male rats.

In this study, thirteen male rats aged 18 months were randomly assigned to three groups: control (n = 10), endurance training (n = 10), and resistance training (n = 10). Training programs were done 5 sessions per week for 8 weeks. Then, all subjects were anesthetized 48 hours after the experiment finished and sampling was performed from the bicep. Then, the expression of AKT and FOXO3 genes was measured using the reference gene by Real-Time PCR method. Finally, statistical analysis was conducted using a one-way analysis of variance, and the pairwise differences were evaluated using Tukey's test.

The results of the analysis variance of FOXO3 and AKT proteins values showed that there is a significant difference between resistance, endurance, and control training groups respectively. Tukey's test for both proteins showed that there is a significant difference between resistance and control groups, and resistance training has a greater effect than endurance training.

Overall, the present study showed that resistance exercises in skeletal muscle can activate autophagy pathways more than endurance exercises. Therefore, resistance training seems to be a more effective training method in improving the expression of genes involved in advancing sarcopenia with aging.

Endometriosis is a systemic endocrine, immunological and gastrointestinal disease. In the pathogenesis of endometriosis, various cellular pathways are involved. One of these pathways is autophagy. The aim of this study was to evaluate the expression of BECLINE-1 and LC3 genes in endometriosis mice following regular aerobic exercise and omega-3 intake. 

In this experimental study, 35 adult male Wistar rats were randomly divided into healthy control groups, endometriosis, endometriosis+exercise, endometriosis+omega 3, endometriosis+omega3+exercise after creating an endometriosis model. Were. The duration of training in water was 30 minutes daily until the end of the training period. At the same time, the mice received omega-3 supplementation daily in the form of gavage at a dose of 2 ml/kg. One-way analysis of variance was used to analyze the data.

The results showed that the expression of BECLINE-1 and LC3 genes in the endometriosis group had a statistically significant increase compared to the healthy control group. All three groups of endometriosis+exercise, endometriosis+omega, and endometriosis+exercise+omega had a statistically significant decrease compared to the endometriosis group. The endometriosis+exercise+omega group decreased more than the other groups.

In general, the results of the present study indicate that the increased expression of autophagic genes produced in endometriosis can be inhibited by regular aerobic exercises such as swimming and omega-3 supplementation. Pathological disorders in autophagy with exercise and omega-3 supplementation may help improve endometriosis by regulating the expression of LC3 and Beclin-1 genes.

Autophagy is lysosomal degradation pathway that contributes to tumor development through metabolic support, especially at final stages. The purpose of this study was to evaluate the effect of 12 weeks endurance training on autophagy-related gene expression levels in tumors of breast cancer-bearing BALB/c mice.

Twenty-two female BALB/c mice were randomly divided into control (n= 11) and experimental (n= 11) groups. Breast cancer was induced by injecting MC4-L2 cancer cells into the right dorsal mammary fat pad. The experimental group underwent training protocol for 12 weeks. Expression levels of autophagy-related genes were measured by real-time PCR and quantified bymethod. Data analysis was done applying Student t-test.

Endurance training led to significant decrease in tumor weight (P= 0.038) and volume (P= 0.043) in experimental group compared to the control group. Expression levels of Beclin1 (11%), Atg7 (53%), p62 (37%), gabarapl (76%), LC3-I (35%), and LC3-II (62%) in tumors of experimental group were lower compared to the controls. In addition, training protocol resulted in a decrease in LC3-II/LC3-I ratio (42%) and increase in p62 expression level (157%) (all P< 0.05).

Endurance training-induced reduction in tumor weight and volume was coincided with substantial reduction in expression levels of autophagy-related genes. This may suggest that beneficial effects of endurance training in breast cancer, at least in part, could be mediated through suppression of autophagy process in solid tumors.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and the third cause of cancer-related death worldwide based on a recent update of Globocan in 2020. The induction of programmed cell death (apoptosis) in tumor cells is one of the main targets of conventional therapies in cancer. One of the key mechanisms that impacts tumor cells apoptotic response is autophagy. Autophagy is a conserved lysosomedependent degradation process that aids in the maintenance of cell homeostasis and metabolic compatibility. Apoptosis and autophagy are two main processes in controlling cell death and survival. Enhanced autophagy at various stages of HCC is related to increased tumor cells survival and malignancy development, allowing cancer cells to evade apoptosis. Various studies that investigated the effect of autophagy inhibition on apoptosis induction in HCC cells indicated that apoptosis inducers have a stronger therapeutic impact after autophagy inhibition. In this study, the crosstalk between autophagy and apoptosis in cells survival, as well as targeted alterations in the balance between these processes in HCC therapy are investigated.

In high-fat diet-induced obesity, the levels of cathepsin L (CTSL) and cathepsin B (CTSB) increase in adipocytes, resulting in insulin resistance in the adipose tissue. In this study, the preventive effect of endurance training on the gene expression of CTSL and CTSB was investigated in the adipose tissue of mice with a high-fat diet.

Twenty-one male mice (age: four weeks, weight: 12 g) were assigned to three groups, including control (n=7), high-fat diet (HFD) (n=7), and endurance training/high-fat diet (ET-HFD) (n=7). The mice of the HFD group were fed HFD (42% fat) for 12 weeks. The mice in the ET-HFD group, along with HFD feeding, were submitted to continuous endurance training on a treadmill for six weeks (five sessions per week), with a progressive increase in intensity and volume. The real-time polymerase chain reaction (PCR) assay was used to assess the gene expression of CTSL and CTSB.

The HFD was fattening (P=0.001). The gene expression of CTSL did not significantly change in the groups (P=0.118). However, the gene expression of CTSB increased fivefold in the HFD group as compared to the control group (P=0.001). The increase in the level of CTSB was 50% lower in the ET-HFD group compared to the HFD group (P=0.013).

Endurance training could partially prevent the upregulation of CTSB induced by a high-fat diet. It seems that the preventive effect of endurance training against obesity-related complications is partly due to the inhibition of CTSB expression in the adipose tissue.

Autophagy plays an important role in the aging process. Exercise is known to be one of the most important modulators of aging; however, the effects of high-intensity interval training (HIIT) on autophagy are not well known. Therefore, this study aimed to investigate the effect of HIIT on protein levels of sestrin 2, AMPK, beclin1 and ULK1 in skeletal muscle of elderly rats.

Twenty-old male Wistar rats (18 months) were randomly divided into experimental and control groups. After estimating the maximum speed, rats in the experimental group participated in 8 weeks of high-intensity interval training of running on the treadmill (5-8 sets of running for 2 minutes at an intensity of 80-100 VO2Max with rest intervals of running for 2 minutes at an intensity of 50 VO2Max) five sessions per week. Skeletal muscle tissue samples were extracted 48 hours after the last training session to measure protein levels of factors assessed. An independent t-test was used to analyze the data and p < 0.05 was considered significant.

HIIT resulted in a significant increase in protein levels of sestrin 2 (P=0.01), p-AMPK (P=0.005), beclin1 (P=0.001), and ULK1 (P=0.03) in the experimental group compared to control one.

It seems that HIIT can play a regulatory role in autophagy through the sestrin 2 / AMPK pathway and modulate subsequent progression of changes associated with aging in the skeletal muscle of elderly rats.

Due to proven anti-tumor activity of quercetin (QT), however the low effectiveness of QT has restricted its use. This study aimed to assess the toxic effect of QT encapsulated in solid lipid nanoparticles (QT-SLNs) on the cell death (Autophagy) of MCF-7 human breast cancer cells.
 

MCF-7 and MCF-10A (non-tumorigenic cell line) cell lines treated with 25 µml/mL of QT or QT-SLNs for 48 h. Cell viability and Autophagy were evaluated to determine the toxic effectiveness of the QT-SLNs.

The QT-SLNs with appropriate characteristics were prepared. The QT-SLNs showed sustained QT release until 48 h. Cytotoxicity assessments indicated that QT-SLNs inhibited MCF-7 cells growth with a low IC50 (50% inhibitory concentration) value, compared to the free QT. QT-SLNs induced a significantly increased in Autophagy in the MCF-7 cells. Following QT-SLNs treatment, the expression of the ATG-5 protein significantly increased in comparison with free QT-treated cells. Furthermore, The QT-SLNs significantly increased autophagy indexes in MCF-7 cells. Viability and autophagy of MCF-10A cells were not affected by QT or QT-SLNs.

According to these results, SLN significantly enhanced the toxic effect of QT against human breast cancer cells.

Cancer is a multi-faceted diseases caused cell proliferation in an out of control manner due to accumulation of defects and mutation in their DNA and with an impendence to invade or spread to parts of the body. During last decades new compounds with natural roots have emerged as a new paradigm for effective anti-cancer treatment.

The aim of this study is to evaluate the potential of ergolide a sesquiterpene lactone with multi-functional history to induce apoptosis.

Ergolide from Inula-Oculus-Christi a sesquiterpene lactone from Asteraceae plant was extracted by Traditional Medicine Research Center of Shahid Beheshti University of Medical Sciences. The cytotoxic effects of Ergolide on the acute lymphoblastic leukemia (MOLT4) and PBMC (normal cell line) were investigated at different doses for 48 hours. In this study, MTT assay and acridine orange staining were used. Also, annexin V-PI assays was utilized for further evaluation. In addition the gene expression level of BAX and BCL2 were analyzed by q-RealTime-PCR (quantitive RT-PCR).

The results of MTT assay demonstrated the induction of apoptosis and reduction in proliferation of MOLT4 cells treated by ergolide. (P < 0.001). Interestingly Ergolide could be less toxic in normal cells (PBMCs). AO staining and Flow cytometry analysis confirmed a significantly high percentage of autophagic and apoptotic cells compared with control groups respectively (P < 0.05).

According to the results, ergolide demonstrated cytotoxic effects on MOLT-4, but further studies are needed to confirm its effectiveness as a complementary agent in the treatment of acute lymphoblastic leukemia.

Autophagy is a new therapeutic strategy aimed at reducing the diabetic abnormalities. While excessive or insufficient autophagic activity during diabetes leads to altered cellular homeostasis. So, aim of the present study was conducted to determine the effect of eight-week high-intensity interval training (HIIT) along with caffeine injection on the levels of some myocardial autophagy-related proteins in diabetic rats.

In experimental design, fifty male white wistar rats with an age range of 3-2 months  (average weight 250±25 g) were randomly divided into 5 groups of homogeneous 10 rats in each group: Healthy control (C: intraperitoneal injection of saline), Diabetic control (D: high-fat diet combined with a single intraperitoneal injection of streptozotocin, Diabetic with training (D+T: running with intensity at the 85-90% of maximum speed in 5 to 12 bout of 2 min-1; 5 days/week for 8 weeks), Diabetic with caffeine supplementation(D+CA: intraperitoneal injection of pure caffeine at 70 mg.kg-1 5 days/week for 8 weeks), Diabetic with training and with caffeine supplementation (D+T+CA). For evaluate changes in the expression profile of some of the genes associated with autophagy signaling pathway (LC3-II, ULK-1, Beclin1) in the myocardium (left ventricular), based on Western blot analysis will be used. Also, the one-way analysis of variance (ANOVA) and Tukey post hoc test were be used to analyze the data.

The expression of all autophagic proteins in diabetic with trained and non-trained groups was higher than in healthy
group (P≤0.05). On the one hand, the expression of autophagy-related proteins in the trained group with caffeine supplementation was significantly higher than that of the training group without caffeine intake (P=0.001).

The findings of this study suggest that caffeine injection exacerbated the expression of autophagic proteins induced by diabetes; On the other hand, high-intensity interval training can as a preventive strategy, modulate diabetes-induced myocardial autophagy.