apoptosis

 Helicobacter pylori infection is known as the main risk factor associated with chronic gastritis and gastric adenocarcinoma. Extracellular vesicles are among the key virulence factors of this bacterium, which play a role in inducing inflammation and inhibiting the apoptosis process in host cells. Probiotic strains, including Lactobacillus species, can play a role in inducing the process of cellular apoptosis. This study aimed to evaluate the effect of L. gasseri ATCC 33323 on the apoptosis process in AGS cells treated with extracellular vesicles (EVs)  of H. pylori.

EVs were isolated from two clinical strains of H. pylori (BY-1 and OC824). The morphology of EVs was identified by transmission electron microscopy and dynamic light scattering. The viability of AGS cells was examined in the presence of various amounts of H. pylori EVs and L. gasseri cell-free supernatant (CFS). Based on the MTT assay, 50 μg/mL of H. pylori EVs and 10% v/v of L. gasseri CFS were used for further experiments. Apoptosis was investigated using RT-qPCR targeting key apoptosis mediators (BAX, CASP3, CASP8, CASP9, BCL2, and NOD1).

H. pylori EVs were identified in the size range of 50-200 nm. Based on the results of cell viability assays in AGS cells, 50 micrograms per milliliter of H. pylori extracellular vesicles and 10% (v/v) of L. gasseri culture supernatant were used for cell treatment. H. Pylori EVs downregulated the gene expression of BAX, CASP3, CASP8, and CASP9 and upregulated BCL2, and NOD1 in AGS cells at 12 and 24 h. In contrast, L. gasseri CFS effectively induced cell apoptosis, which was inhibited by EVs.

The present study showed that L. gasseri CFS can effectively induce H. pylori EV-inhibited apoptosis in AGS cells. Further research is needed to elucidate the precise function of L. gasseri CFS and its metabolites in the induction of apoptosis.

Cells are continuously exposed to various cellular stresses. Over 50% of human cancers carry mutations in the p53 gene, therefore p53 has been considered a critical tumor suppressor. Upon DNA damage, p53 accumulates in the cellular nucleus through post-translational modifications. 

In this study, the impact of an acidic and conditioned MDA-MBA231 breast cancer environment on the pathways of apoptosis and parthanatos in normal fibroblast cells was examined. The expression of Bcl2, Bax genes involved in apoptosis, PARP1, PARG genes involved in parthanatos, and p53 protein was evaluated. Moreover, the electrophoresis method was used to study DNA breakage in normal, acidic, conditioned, and acidic plus conditioned media.

The results showed that the level of DNA damage in acidic and conditioned media was less than that in conditioned media and higher than that in normal and acidic media. Although conditioned media induced less Bax and Bax/Bcl2 ratio than other media in fibroblasts, there was no significant difference between the Bax/Bcl2 ratio in other groups as the apoptosis index. PARP1 and PARG gene levels were the lowest in conditioned plus acidic media, and p53 was downregulated in conditioned media.

Parthanatos and the level of Bax were not responsible for DNA damage in conditioned media, whereas a decrease in p53 was partly associated with poor DNA repair under stress conditions in cancer cells in normal fibroblasts.

  Developing therapies that promote the efficient death of cancer cells by apoptosis has been a cornerstone and goal of clinical oncology for over thirty years. Multiple signaling pathways, known as intrinsic and extrinsic, are involved in the process of programmed cell death. These pathways are activated by various stimuli such as immune surveillance, DNA damage and cellular stress. Cell death may also be influenced by how apoptotic pathways interact with other signaling processes. Drug discovery studies (Addressing bioavailability, stability, tumor penetration, toxicity profile in non-malignant tissues, drug interactions, and off-target effects) and an understanding of tumor biology are essential for the clinical translation of effective pro-apoptotic agents. Tumor cell death is possible with therapeutic methods, but the selection, growth and proliferation of resistant cells ultimately determine the lethality potential. The present study aimed to investigate the early apoptosis pathways and the related signaling pathways, along with discussing their molecular targets in terms of therapy.

The aim of this study was to investigate the effective genes on apoptosis (BAX and Bcl2) in liver and intestinal cells of broiler chickens fed silver nanoparticles coated on clinoptilolite under acute heat stress induction. 450 d old broiler chicks (Cobb 500) were used in five treatments and six repetitions, and 15 pieces were used in each experimental unit in the form of a completely random design. Experimental diets were: 1) control or basal diet 2) basal diet supplemented by 1% clinoptilolite 3) basal diet supplemented by 1% clinoptilolite coated with 0.5% nanosilver 4) basal diet supplemented by 0.15% organic acid and  5) basal diet supplemented by 1% clinoptilolite coated with 0.5% nanosilver and 0.15% organic acid. Silver nanoparticles coated on clinoptilolite were investigated using XRF and FTIR techniques. In order to induce heat stress, the birds were affected by heat stress for one week in the last week of the breeding period, and on the last day of the stress, liver and intestine samples were obtained to check gene expression. The results of this experiment show that the treatments of clinoptilolite and silver nanoparticles coated on clinoptilolite have an increasing effect on the expression of Bcl2 and Bax, while this effect was not seen in the organic acid treatment. In conclusion, it could be said that if silver nanoparticles are used in feeding livestock and poultry, it is better to use organic acid supplements to reduce the side effects of silver nanoparticles.

Mitochondria is one of the dynamic organelles in the cell, the dysfunction of which weakens the function of the cell and ultimately causes cell death. Mitophagy is the selective autophagy of damaged mitochondria, which improves cell biological functions by removing dysfunctional mitochondria. The PINK1-Parkin signaling pathway is one of the most important mitophagy regulation pathways. The PINK1-Parkin signaling pathway is one of the most important mitophagy regulation pathways. Disruption of mitophagy is the main cause of many metabolic, neurodegenerative diseases, cancers and aging. The evidence obtained from human and animal studies shows that aerobic exercise develops mitochondrial mitophagy by regulating and activating signaling pathways and maintains health at the cell level, thereby reducing the incidence of diseases. Although the exact molecular mechanism of the effect of aerobic exercise on the development of mitochondrial mitophagy is not known, the results of several studies show a reduction in oxidative stress, inflammation, apoptosis, and an increase in anti-inflammatory myokines along with regular aerobic exercise by activating mitophagic signaling pathways, especially the PINK1 signaling pathway. -Parkin regulates mitophagy in various tissues and in the conditions of old age, obesity, inactivity and metabolic disorders and prevents the development of many diseases. The regulatory role of aerobic exercises on mitophagy emphasizes the effectiveness of these exercises on tissue protection and health development.

Nanoparticles due to their wide applications in medicine,industry,and biotechnology, have attracted many scientists’ attentions. Recently, nanoparticles especially selenium nanoparticles are widely used to diagnosis and cancer treatment. The aim of this study was to evaluate the cytotoxic and anticancer effects of selenium nanoparticles on colon cancer cell line and analysis of CAD (Caspase Activated DNase) gene expression.

In this study, colon cancer HT29 and normal HEK293 cell lines were purchased from the Pasteur Institute Cell Bank of Tehran and treated with selenium nanoparticles overnight. The cells were cultured in Dulbecco’s Modified Eagle’s Medium (DMEM) (Gibco, Scotland) medium with 10% FBS serum and 1% streptomycin antibiotic (Gibco, Scotland). The cells were then stored at 37 ° C. In this study, cytotoxic effect of Selenium NPs was evaluated on HT29 and HEK293 cells using MTT (3-(4, 5-Dimethyltetrazollium Bromide) assay. Subsequently, they were treated with selenium nanoparticles in different concentrations (0, 7.81, 15.62, 31.25, 62.5, 125, 250 and 500 mg/mL) for 24 hours. To solubilize the viable cells formazan crystals production, we added 100 μl/well of dimethyl sulfoxide (DMSO) to them. After treatment of HT29 cells with IC50 concentration, the total RNA was extracted and cDNA synthesized. Moreover, CAD gene expression was evaluated using Real Time PCR method. The data was evaluated by ABI StepOne utilizing the Applied Biosystems qRT-PCR (ABI 7300 system, Applied Biosystems). The quantification of the mode of Selenium NPs -induced cell death in the HT29 cells were ascertained using flow cytometry followed by staining with fluorescein isothiocyanate (FITC)‐Annexin V and propidium iodide (PI) staining. Finally, the study of apoptosis and necrosis of Selenium NPs was evaluated using flow cytometry method. Data analysis was statistically determined by using One-way analysis of variance (ANOVA) with SPSS/22 software followed by a Tukey test.

The result showed that the treatment of Selenium NPs at 31.25 to 500 µg/mL concentration had maximum cytotoxic effect, revealed statistically significant (P˂0.001). The IC50 value for Selenium NPs were measured at 75 µg/mL after 24 hours. In order to determine the effect of Selenium NPs on cancerous cells, alterations in the mRNA expression levels of CAD gene in HT29 cells were done by qRT-PCR technique followed by the exposure to nanoparticle. The CAD gene expression comparing to reference gene was up-regulated 4.04±0.125 fold. To determine the mechanism of cell death in the cancer cells, annexin V/PI flow cytometry was carried out. In the treatment of HT29 cells by IC50 of selenium NPs, 10.43%, and, 24.28% of early and late stages’ apoptosis were observed, respectively

Our results suggest that selenium NPs can display some promising cytotoxic properties through inducing apoptosis pathway. Based on the results, up-regulated gene expression involved in apoptosis (CAD) and activating apoptosis, it can be concluded that the selenium NPs can be used as drug candidate in colon cancer treatment, but more studies are needed regarding the medicinal importance of nanoparticles.

Organotypic cultures of spinal cord slices from mammalian neonatal and fetal animals are powerful tools for studies of spinal cord injury, neuronal degeneration, and cell death but also motor neuron regeneration. Models in which adult slices are used would be very useful. However, adult spinal cord slices are notoriously difficult to maintain in culture and rapidly deteriorate in vitro. Degeneration of motor neurons in the spinal cord is a critical phenomenon in spinal cord injuries and certain neurodegenerative diseases such as amyotrophic lateral sclerosis, a neurodegenerative disorder in which motor neurons in the spinal cord and motor cortex are lost. A variety of mechanisms have been proposed as having a role in neuronal apoptosis during spinal cord injury. Oxidative stress has been reported as one of the mechanisms involved in the apoptosis of motor neurons in spinal cord injuries and neurodegenerative diseases. This study was conducted to determine whether quercetin, as a potent antioxidant, can delay apoptosis in motor neurons of cultured spinal cords by reducing oxidative stress. 

The thoracic regions of the spinal cord from adult NMRI mice were sliced using a tissue chopper and divided into three groups: 1) 0-hour, 2) control group, and 3) group treated with quercetin (100 µM). Spinal cord slices in the 2 and 3 groups were incubated for 6 hours at 37°C in a Co2 incubator. The viability of the spinal cord slices was measured using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The morphological features of apoptosis and the number of motor neurons were examined using Hoechst and propidium iodide staining. The malondialdehyde was measured to determine lipid peroxidation while the FRAP (ferric reducing antioxidant power) was assessed to evaluate total antioxidant capacity in fresh and cultured spinal cord slices. Results were expressed as mean±SD. One-way analysis of variance (ANOVA) followed by Tucky’s test was used to assess the statistical significances of the data. In all cases, a statistical probability of p<0.05 was considered significant.

After 6 hours (control group) in culture, the viability of the spinal cord slices, the neuron diameter, and the number of healthy motor neurons significantly decreased compared to the 0-hour group. Also, motor neurons showed the morphological features of apoptosis including cell shrinkage, nuclear and chromatin condensation in the control group. A significant increase in the amount of malondialdehyde and a significant decrease in the total antioxidant capacity was also observed compared with the 0-hour group. After 6 hours, quercetin not only increased the viability and the number of healthy motor neurons in the cultured slices but also reduced the morphological features of apoptosis in the motor neurons compared with the control group. In addition, quercetin significantly reduced the amount of malondialdehyde and increased the total antioxidant power in slices cultured for 6 hours.

Oxidative stress might be considered as one of the mechanisms involved in the apoptosis of motor neurons in cultured spinal cord slices and quercetin, as a potent antioxidant, was able to increase the viability of the cultured spinal cord slices and delay the morphological features of apoptosis in the motor neurons through reducing lipid peroxidation and increasing the total antioxidant capacity.

Cancer is abnormal cell proliferation and uncontrolled cell growth. Carcinogenic factors cause DNA damage, decrease the function of tumor suppressor gene and cause tumor and metastasis. Some of the causes of cancer are physical factors such as ultraviolet rays, chemicals, cigarette smoke, unbalanced diet, occupational factors, heredity, hormones, metabolic factors, and biological factors, especially some bacteria and viruses. The most important method of cancer treatment is chemotherapy, which has many side effects and causes drug resistance. Some plants have been known for years as a reliable and excellent source of anticancer agents for production of anticancer drugs. Some plants have preventive and therapeutic effects against cancer, and some of them can reduce side effects of chemotherapy and radiotherapy, and are also economical. One of the most important natural compounds in plants having anticancer properties are phenolic compounds. Phenolic compounds are classified into different groups such as simple phenole, flavonoids, coumarins, phenolic acids, stilbenes and antraquinones. The mechanism of anticancer effect of most of these substances is related to their antioxidant property and inhibiting the growth of tumor cells. Many of these compounds are traditionally used in different regions of the world. In this review article, phenolic compounds with anticancer properties will be investigated and the most important mechanisms of their effects will be introduced. We hope that this article will provide readers with useful information to understand the potential of plants in producing new anticancer compounds and encourage researchers to undertake projects leading to development of new natural anticancer drugs.

Cancer remains a global health problem, with ovarian cancer ranking fifth among cancers affecting women and the leading cause of cancer-related death in women. There are different types pf ovarian cancer, including Epithelial ovarian cancer, Stromal tumors and Germ cell tumors.  Epithelial ovarian cancer is the most common type that includes several subtypes, including serous carcinoma and mucinous carcinoma. To this end, several factors have been identified to increase your risk of ovarian cancer, including older age, inherited gene changes, family history of ovarian cancer, being overweight or obese, postmenopausal hormone replacement therapy, endometriosis, and never having been pregnant. The current strategies to treat ovarian cancer include surgery, chemotherapy, radiotherapy and targeted therapies, and hormone therapy. Scientists continue to investigate the foundational mechanisms involving cancer development, as well as to find new drugs and metabolites having the capacity to control cancer. Alpha-ketoglutarate (AKG), a critical metabolite in the Krebs cycle involved in cellular energy production and the regulation of gene expression. Recent studies have shown that AKG may have the potential to enhance the efficacy of cancer treatments, by modulating the tumor microenvironment and improving the immune response against cancer cells. This study investigates the effect of AKG on ovarian cancer cells.

SKOV3 cells were obtained from Tehran University and cultured in complete culture medium (RPMI, 10% Fetal bovine serum (FBS), and 1% Penicillin-Streptomycin (Pen/Strep)). To find the proper concentration of AKG, SKOV3 cells were cultures in 96-well plate, and treated with different concentration of AKG (range 20 to 220 µM). After 24 and 48 h, the viability of the cells was determined using MTT assay. Based on the results obtained from viability assay, 200 μM of AKG was selected for the next assessments. To evaluate the effect of AKG on SKOV3 cell proliferation using plotting a growth curve, cells were cultured in the presence (200 μM AKG) and absence of AKG, and counted the number of cells every 24h for one week. To determine the population doubling time (PDT), the cells were cultured in the presence (200 μM AKG) and absence of AKG for 72h, then the cell were collected and the number of living cells was counted using Neubauer Chamber. The PDT was calculated using a related standard method. To assess colony formation potential, the SKOV3 cell were cultured in the presence (200 μM AKG) and absence of AKG. After 7 days, the cells were fixed using 10% formalin solution, then the colonies were stained using crystal violet dye, and the number of colonies were counted using inverted microscope. To investigate the effect of AKG on the migration rate of SKOV3 cells, the cells were cultured in complete medium to reach 85% confluence, then treated with mitomycin (10 μM) for 3h, then Created a scratch in the cell monolayer using a sterile pipette tip. the cells were cultured in the presence (200 μM AKG) and absence of AKG for 3 days. The images of the scratch were taken at regular intervals using a microscope, and the closure of the scratch over time was analyzed. To analyze the cell cycle profile, the SKOV3 cell were cultured in the presence (200 μM AKG) and absence of AKG for 48h. Then, the cells were collected and analyzed using a flow cytometry.

Based on the MTT assay, 200 μM AKG was determined as the proper concentration to investigate other biological behaviors of SKOV3 cells. Colony forming assay showed a decrease in the number and size of colonies in the AKG-treated group (P<0.05). In addition, the cell doubling time increased in the treatment group, indicating slower growth rate (P<0.05). Growth curve analysis confirmed reduced cell growth in treated group. Cell cycle analysis showed a higher percentage of treated cells arrested in S and G1 phases. The scratch assay showed slow cell migration and metastasis in the cells treated with 200 µM AKG.

In conclusion, AKG has an inhibitory effect on the proliferation, viability, migration in SKOV3 ovarian cancer cells, highlighting its potential as an adjuvant treatment with existing therapies. More research is necessary to fully investigate the therapeutic effect of AKG in ovarian cancer.

Non‑small cell lung cancer (NSCLC) patients have a frequently poor prognosis and current therapies have large side effects. Numerous studies have been focused on the anti-cancer effects of melittin. Concerning the anti-cancer effects of melittin, this study aimed to evaluate melittin's anti-cancer effects on Calu-3 lung cancer cell line.

Cytotoxicity of melittin on Calu-3 and MRC5 cells was assessed using MTT assay. Real-Time PCR was used to determine expression of apoptotic and pro-apoptotic BAX, BCL2, and CASP3 genes. Furthermore, a wound healing assay was performed to compare the inhibition effects of melittin on the migration of interested cells.

IC50 values of melittin for Calu-3 and MRC5 were respectively 1.67μg/mL and 3.44μg/mL after 24h. Expression levels of BAX and CASP3 increased ‘2.82 and 4.31’ and ‘1.58 and 4.07’ fold in Calu-3 and MRC5, whereas BCL2 gene expression decreased 0.64 and 0.35-fold in the mentioned cell lines. It is demonstrated that cell migration is inhibited by melittin.

Melittin has an anti-cancer effect on Calu-3 lung cancer cell line. Furthermore, melittin induces apoptosis and inhibits cell migration of lung cancer cells. Melittin increases the apoptotic gene expression level and eventually causes the cells to move toward cell death. In addition, comparing the effects of melittin on Calu-3 cancer cells and MRC5 normal cells, it can be concluded that melittin has inhibitory and apoptotic effects on cancer cells at lower doses.

The aim of this study was to investigate the response of beta-cateninand bax gene expression in liver tissue of mice with melanoma to a period of aerobic exercise with nettle extract.

In this study, 20 adult male rats were randomly divided into 4 groups including: control, exercise, extract and exercise + extract. The training program consisted of 30 minutes of running on a treadmill without a slope at a speed of 16 meters per minute for the first week, and one meter per minute was added every week until it reached 22 meters per minute in the eighth week. One week after melanoma induction, the experimental group consumed 30 mg / kg / day of nettle ethanolic extract orally for 8 weeks. RT PCR was used to measure the expression of beta-cateninand baxgenes.

Data analysis showed that Beta-catenin gene expression was increased in the experimental groups compared to the control group; But did not reach a significant level (p = 0.103). The results also showed that BAX gene expression was significantly reduced in the experimental groups compared to the control group (p = 0.026).
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The results show that consumption of nettle extract along with aerobic exercise by reducing BAX levels and increasing beta-catenin in activating the WNT / beta-catenin signal pathway and apoptosis has an immune stimulus to prevent tumor growth and cancer progression.

Diabetes is a chronic disease that affects the metabolism of sugar or blood glucose. This disease is caused by insulin resistance in the body. Diabetes can lead to various complications in the body, including liver damage. Berberine reduces the amount of damage caused by oxidative stress on mitochondria and increases the antioxidant capacity of liver tissue. exercise training causes mitochondrial biogenesis in diabetic patients. Therefore, the aim of this study was to investigate the effect of aerobic exercise with different doses of berberine chloride on the apoptosis of liver cells in diabetic male rats with streptozotocin.

In this experimental study, 64 male Wistar rats were randomly divided into 8 groups of 8. The groups include the control group, diabetic, diabetic and taking berberine chloride with a dose of 15 mg/kg, diabetic and taking berberine chloride with a dose of 30 mg/kg, diabetic with aerobic exercise, taking berberine chloride with a dose of 15 mg/kg, diabetic with aerobic exercise and the consumption of berberine chloride with a dose of 30 mg/kg, diabetics with aerobic exercise and the control group with aerobic exercise were divided. Intraperitoneal injection of streptozotocin 60mg/kg was used to make diabetic groups diabetic. Berberine chloride (15 and 30 mg/Kg) was taken orally by gavage once a day. The exercise groups performed aerobic exercise for 6 weeks with an intensity of 50-55% of maximum oxygen consumption. 48 hours after the last training session, the liver tissue was extracted to check the changes of caspase3 protein. Using the TUNEL method, the amount of apoptosis in the liver tissue was evaluated. Data were analyzed using one-way analysis of variance and Tukey's follow-up test.

In the present study, diabetic rats showed a significant increase in liver tissue apoptosis and caspase3 protein expression. Treatment of diabetic animals with berberine in doses of 15 and 30 mg/kg led to a significant reduction of apoptotic cells in diabetic rats. The expression of caspase3 protein in the diabetic group with aerobic exercise and berberine chloride consumption at a dose of 30 mg/kg was significantly decreased compared to the diabetic group and berberine chloride consumption at a dose of 15 mg/kg.

It seems that the treatment of diabetic rats with berberine chloride together with exercise activity was able to prevent the occurrence of apoptosis in the liver tissue and improve the liver damage caused by diabetes.