Bcl-2 Gene Expression Levels Research Articles

Curcumin-Etoposide Synergy: Unveiling the Molecular Mechanisms of Enhanced Apoptosis and Chemoresistance Attenuation in Breast Cancer

Background: Combining natural compounds with chemotherapeutic agents has emerged as a promising approach for cancer treatment. Curcumin (Cur), a natural polyphenol, is known for its anti-cancer properties, including the ability to induce apoptosis and arrest cell cycle progression. Objectives: This study aimed to evaluate the effects of Cur and etoposide (ETO), both individually and in combination, on the induction of apoptosis in breast cancer (BC) cell lines. Methods: The impact of Cur and ETO on cell proliferation was assessed using MTT viability assays. Apoptosis induction by these drugs was evaluated through Annexin V flow cytometry and caspase-3 and caspase-9 activity assays. Quantitative real-time PCR was employed to measure Bax and Bcl-2 gene expression levels. Western blotting was conducted to determine protein levels of p53, p21, Bax, and Bcl-2. Results: A non-significant dose of ETO was selected based on MTT assay results and combined with 75 µM of Cur. Curcumin enhanced ETO’s pro-apoptotic effect by increasing caspase activities. The combination of Cur and ETO significantly reduced Bcl-2 gene expression while upregulating Bax expression. Furthermore, treatment with this combination elevated the protein levels of p53, p21, and Bax, compared to ETO or Cur alone, while significantly decreasing Bcl-2 protein levels. Conclusions: Cur has the potential to amplify ETO-induced apoptosis in BC cells. This combination may offer a promising therapeutic approach for BC.

Pterostilbene suppresses head and neck cancer cell proliferation via induction of apoptosis.

Head and neck cancer (HNC) is one of the most prevalent causes of death worldwide, and so discovering anticancer agents for its treatment is very important. Pterostilbene (PS) is a trans-stilbene reported to be beneficial in managing various cancers. The objective of the study was to evaluate the cytotoxic, antiproliferative, proapoptotic, and antimigrative effect of PS on HEp-2, SCC-90, SCC-9, FaDu, and Detroit-551 cell lines. MTT and live/dead assays were employed to assess cell viability, while a cell migration test was performed to evaluate wound healing capacity. The mRNA, protein, and intracellular expression levels of CASP-3, BAX, and BCL-2 genes were evaluated by real-time PCR, western blotting, and immunofluorescence staining. Annexin V-PI staining was conducted to assess the amounts of viable, apoptotic, and necrotic cells. The results revealed that PS displayed cytotoxic, antiproliferative activity in a dose-dependent manner in HNC cells by upregulating CASP-3 and BCL-2 while downregulating BCL-2 in the apoptotic pathway. The proapoptotic properties were confirmed by the annexin-V-IP results. Moreover, PS displayed a significant suppressive efficacy on the migration capacity of HNC cells. The present study provides proof that PS has the prospective to be improved as an attractive anticancer agent against HNC following advanced studies.

Dendrosomal Curcumin Showed Cytotoxic Effects on Breast Cancer Cell Line by Inducing Mitochondrial Apoptosis Pathway and Cell Division Arrest

Background: Mutations in the p53 gene have been linked to the initiation and progression of breast cancer, as well as resistance to chemotherapy. Therefore, the development of novel treatment approaches is essential to combat this disease. Objectives: This study aimed to evaluate the effects of dendrosomal curcumin (DNC) on the breast cancer cell line MDA-MB231. Methods: MDA-MB231 cells were treated with 20 μM DNC, and the apoptosis rate and cell proliferation cycles were assessed using flow cytometry. Additionally, after RNA extraction and cDNA synthesis, the expression levels of Lnc-DANCR, EZH2, Noxa, bcl-2, bax, PUMA, p21, and p53 genes were analyzed using RT-PCR. Protein expression levels of P53, P21, Bcl-2, and Bax were evaluated through western blotting. Results: Dendrosomal curcumin induced apoptosis in MDA-MB231 cells and caused cell cycle arrest at the SubG1 phase. Dendrosomal curcumin treatment downregulated Lnc-DANCR, EZH2, bcl-2, and p53 gene expression, while upregulating bax, Noxa, PUMA, and p21 gene expression in a time-dependent manner. Bax and P21 protein levels were significantly upregulated following DNC treatment, whereas Bcl-2 and P53 protein levels were downregulated in DNC-treated breast cancer cells. Conclusions: In summary, dendrosomal nanocurcumin demonstrated potent anti-tumor effects against breast cancer cells, suggesting its potential as a therapeutic agent in breast cancer treatment.

Exploring the effects of naringenin on cell functioning and energy synthesis in the hippocampus of male Wistar rats with chronic tinnitus, by examining genetic indicators such as Bax, Bcl-2, Tfam, and Pgc-1α

BackgroundThe pivotal factors, including neural plasticity, oxidative stress, neuronal inflammation, and apoptosis, play a significant role in the pathogenesis of tinnitus. The balance between Bax/Bcl-2 genes is an important factor in determining the rate of apoptosis. Pgc-1α and Tfam genes are fundamental regulators of mitochondrial biogenesis. Naringenin possesses significant antioxidant, neuroprotective, anti-inflammatory, anti-apoptotic, and antiviral properties, and its compounds are effective on cell signaling pathways. AimsIn light of the aforementioned information, we endeavored to evaluate the impact of naringenin on the expression levels of Bax, Bcl-2, Pgc-1α, and Tfam genes in the hippocampus of male Wistar rats with chronic tinnitus. Material and MethodsTo demonstrate the existence of tinnitus, all rats were instructed to complete an “active avoidance test” utilizing a conditioning box. The expression levels of genes mentioned above were assessed using real-time PCR. ResultsThe sodium salicylate at a dosage of 350 mg/kg showed an upregulation in the expression level of Bax and a downregulation in the expression level of the Bcl-2 gene (p < 0.001). Furthermore, the sodium salicylate displayed significantly higher expression levels of Tfam and Pgc-1α (p < 0.001) genes. The naringenin, at a dose of 100 mg/kg, led to a decrease in Bax gene expression (p < 0.05) and an increase in Bcl-2 gene expression (p < 0.05). On the other hand, naringenin restored the expression level of both Tfam (p < 0.001) and Pgc-1α (p < 0.01) genes. ConclusionsOur research findings demonstrate that sodium salicylate-induced tinnitus leads to enhanced apoptosis and mitochondrial biogenesis within the hippocampus. Additionally, our evidence recommends that naringenin can reduce apoptosis effectively and maintain a balanced mitochondrial state.

THIOSTREPTON MODULATES TLR4 EXPRESSION AND INDUCES APOPTOSIS IN MDA MB 231 CELLS: AN IN VITRO AND IN SILICO ANALYSIS

Objective: Toll-like receptors (TLRs) are key pattern recognition receptors involved in tumorigenesis, apoptosis, and metastasis. Triple-negative breast cancer (TNBC) is a highly aggressive malignancy with a poor prognosis. Although the role of TLRs in breast cancer remains underexplored, recent studies suggest targeting TLRs in TNBC could be beneficial. In this study Thiostrepton, an antibiotic and novel inhibitor of TLR7-9 in psoriatic inflammation, was investigated for its effects on TLR3, TLR4, and TLR9 expression in TNBC cells (MDA-MB-231). Materials and Methods: The cytotoxicity of thiostrepton was assessed using the MTT assay. RT-PCR was used to measure gene expression levels of TLR3, TLR4, TLR9, Bax, Bcl-2, Nf-κB, and E-cadherin. Cell morphology changes were analyzed with Acridine Orange/Ethidium Bromide (AO/EtBr) staining. Molecular docking and dynamics simulations examined interactions between thiostrepton and the TLR4-MD-2 complex. Results: Thiostrepton led to a concentration- and time-dependent decrease in cell viability. It significantly inhibited TLR4, Bcl-2 gene expression and increased TLR3, Bax, and Nf-κB levels. The changes in Bax and Bcl-2 gene expression, along with alterations in cell morphology, demonstrated that thiostrepton promoted apoptosis in MDA-MB-231 cells. While TLR9 expression reduction was not significant, thiostrepton notably increased TLR3 expression and decreased TLR4 expression. The three independent molecular dynamics simulations demonstrated that thiostrepton binds stably to the TLR4-MD2 domain, exhibiting a high binding affinity as indicated by the binding free energy calculations. Conclusion: Thiostrepton effectively induces apoptosis and reduces cell viability in TNBC cells. In silico analysis suggest thiostrepton could modulate TLR4, highlighting its potential as a candidate for further research and therapeutic development.

Enhancement of apoptosis in Caco-2, Hep-G2, and HT29 cancer cell lines following exposure to Toxoplasma gondii peptides.

Cancer or neoplasm is a cosmopolitan catastrophe that results in more than 20 million new cases and 10 million deaths every year. Some factors lead to carcinogenesis like infectious diseases. Parasites like Toxoplasma gondii, by its components, could modulate the cancer system by inducing apoptosis. The objective of this investigation is to assess the potential of peptides derived from T. gondii in combating cancer by examining their effects on Caco-2, Hep-G2, and HT29 cell lines. Candidate peptide by its similarity to anticancer compounds was predicted through the computer-based analysis/platform. The impact of the peptide on cell viability, cell proliferation, and gene expression was evaluated through the utilization of MTT assay, flow cytometry, and real-time polymerase chain reaction (PCR) methodologies. The cell viability rate exhibited a significant decrease (p < 0.001) across all cell lines when exposed to a concentration of ≤160 μg. Within the 48-hour timeframe, the half maximal inhibitory concentration (IC50) for HT29 and Hep-G2 cell lines was determined to be 107.2 and 140.6 μg/mL, respectively. Notably, a marked decrease in the expression levels of Bcl2 and APAF1 genes was observed in both the Hep-G2 and HT29 cell lines. These findings indicate that the T. gondii peptide affected cancer cell mortality and led to changes in the expression of genes associated with apoptosis.

Protective Effects of Antimicrobial Peptide Microcin J25 (MccJ25) Isolated From Escherichia coli Against Breast Cancer Cells

ABSTRACTMicrocins are antimicrobial peptides (AMPs) with low molecular weight, which are produced by Enterobacterales and have broad‐spectrum antibacterial activity. Alternative approaches like AMPs could help conventional anticancer treatments to fight malignant cells. The present study endeavors to examine the antitumor activity of microcins isolated from different Enterobacterales strains. In total, 120 Enterobacterales isolates were examined after identification. Subsequently, the bacteria were subjected to an agar diffusion test to assess their antibacterial efficacy. Positive isolates were further examined for the presence of Mccj25 using PCR. The cytotoxic effects of isolates harboring the microcin gene were explored using quantitative real‐time PCR (RT‐qPCR) and the MTT test on breast cancer cells. In addition, the expression levels of BCL2 and STAT3 genes were evaluated, and apoptosis was quantified using flow cytometry. The repair rate of normal cells was determined using a scratch assay. The findings obtained from the phenotypic and biochemical assays have duly verified and established the categorization of the Enterobacterales. After conducting the agar diffusion test, a total of 25 isolates of Escherichia coli and Klebsiella pneumoniae displaying inhibition zones were chosen as suitable specimens possessing AMPs. The analysis conducted on the expression of the Mccj25 gene within the aforementioned isolates indicated that Isolate 83 exhibited significant expression of the Mccj25 gene. The extract obtained from this isolate on the breast cancer cell line exhibited the most significant degree of toxicity after 48 h. Furthermore, the treatment of breast cancer cells with Isolate 83 showed that the rate of apoptosis was about 86%, and the expression of BCL2 and STAT3 genes decreased. Contrarily, it potentiated the reparative ability of nontumoral fibroblasts, supporting the in vitro safety toward normal cells and, at the same time, the selectivity against malignant ones. In summary, our results highlighted a significant growth suppression of breast cancer cells with an escalated rate of cellular demise via the apoptosis pathway.

Effects of platelet-rich fibrin on human endometrial stromal cells behavior in comparison to platelet-rich plasma.

Intrauterine transfusion of platelet-rich plasma (PRP) has become a new treatment for thin endometrium (TE) in recent years, but its low efficacy due to rapid release of growth factors limits its clinical use. Platelet-rich fibrin (PRF) starts the coagulation cascade reaction immediately after the blood comes into contact with the test tube. The natural coagulation process results in stable platelet activation and the slow release of growth factors. In our study, primary human endometrial stromal cells (hESCs) were extracted from endometrial tissue. PRP and PRF were prepared from the patient cubital vein blood. Stromal cells were cultured in conditioned medium supplemented with PRP and PRF. Differences in cell behavior were observed by cell proliferation test and cell migration test. The relative expression levels of apoptotic Bax and antiapoptotic Bcl-2 genes were measured by qRT-PCR. The release of growth factors from PRP and PRF was detected by ELISA. We found that both PRP and PRF inhibited apoptosis of hESCs, which favored cell proliferation and migration. In addition, PRF releases growth factors for a longer period of time compared to PRP. PRF offer a more sustained therapeutic effect compared to PRP, which provides a new idea for endometrial regeneration and repair.

Investigation of apoptotic efficacy of propolis in MCF-7 cell line

Objective: Propolis, also known as bee glue, is a resinous compound collected by honey bees from various plants and processed by their saliva enzymes. Propolis and its components have been studied for their cytotoxic effects on cell lines in vitro, and recent studies have shown that they also have an antitumor effect in vivo. This study aimed to investigate the in-vitro apoptotic effects of propolis on the human breast cancer cell line (MCF-7). Method: The MTT test was used to determine the effect of propolis on cell viability and the doses to be administered. The GraphPad Prism Version 6.01 program was used to analyze the MTT results, while the qRT-PCR method was used to determine the expression levels of Caspase-8, Caspase-9, and Bcl-2 genes. The RT2 profiler PCR Assay Data Analysis version 3.5 was used to analyze gene expression data. Results: This study it was found that doses of 3.9 and 7.8 µg/ml of propolis showed no cytotoxic effect, while doses of 15.625 µg/ml and above had a cytotoxic effect. There was no change in the expression levels of genes at concentrations of 3.9 µg/ml and 7.8 µg/ml of propolis. However, at 15.625 µg/ml of propolis, Caspase-9 gene expression increased 11.89-fold (p=0.033). Although there was no significant difference in Caspase-8 gene expression in the extrinsic pathway of apoptosis (p=0.437), a 0.04-fold decrease in anti-apoptotic Bcl-2 gene expression was observed (p=0.000098). Conclusion: In conclusion, propolis showed a dose-dependent cytotoxic effect on the MCF-7 cell line, induced apoptosis, and did so via the intrinsic pathway of apoptosis. The study suggests that propolis has high potential as an anticancer agent since its apoptotic effects have been demonstrated in the MCF-7 cell line.

Iturin A and Gramicidin A inhibit proliferation, trigger apoptosis, and regulate inflammation in breast cancer cells

Biosurfactants with antibiotic, antiviral, anti-tumor, and immunomodulatory properties appear to have potential in cancer treatment due to their lack of known toxicities compared with conventional chemotherapy. However, there are few studies on the use of biosurfactants for the treatment of breast cancer. In this study, to develop a new strategy for breast cancer treatment, we evaluated the anti-proliferative, anti-inflammatory, anti-tumor, and apoptotic effects of two different biosurfactants (Iturin A and Gramicidin A) from bacillus in both single and binary combination on two breast cancer cell lines (MDA-MB-231 and MCF-7, which is estrogen receptor-negative and positive, respectively). First, the anti-proliferative effects of Iturin A and Gramicidin A, both single and in combination, were explored by MTT assay. Then, the effects of Iturin A and Gramicidin A on inflammatory factors were evaluated using the ELISA method. Apoptosis was assessed using Annexin V-PE/7-AAD and Giemsa staining methods. RT-qPCR analysis was used to evaluate the expressions of several cytokines with anti-tumor and apoptotic properties and the apoptotic BAX and BCL2 genes. Biosurfactants showed anti-proliferative and anti-tumor properties by decreasing the viability of MDA-MB-231 and MCF-7 cells depending on concentration and time (p < 0.05-p<0.01). Biosurfactants induced apoptosis by stimulating apoptotic cell death (p < 0.05-p<0.001) and by increasing BAX and decreasing BCL2 gene expression levels (p < 0.05-p<0.001) in breast cancer cells. Biosurfactants also regulated the expressions of extracellular and intracellular cytokines (IL-2, IL-6, IL-12, IL12RB2, TGFβ, TNFα, VEGF) and chemokines (IL-8, CCL2, CXCL10) in breast cancer cells (p < 0.05-p<0.01). Both single and binary combination applications of Iturin A and Gramicidin A biosurfactants, may potentially treat breast cancer patients, and the in vitro results presented here warrant further in vivo studies.

MicroRNA-145 enhances lung cancer cell progression after exposure to lyophilized fertile hydatid cyst fluid of Echinococcus granulosus sensu stricto

There is increasing evidence that the secretory/excretory antigens of the larval stage of Echinococcus granulosus can induce both anticancer and oncogenic effects between parasite-derived metabolites and various cancer cells. The dual role of miR-145 as either a tumor suppressor or oncogene has already been reported in cancer. However, the mechanism by which miR-145 induces apoptosis in lung cancer cells treated with hydatid cyst fluid (HCF) remains unclear. The fertile HCF was obtained from sheep, purified and lyophilized. H1299 human lung cancer cells were then cultured into two groups: HCF-treated H1299 lung cancer cells and untreated H1299 cancer cells as control cells. Cell viability was assessed using MTT assay to evaluate the effects of HCF on the H1299 cells. Caspase-3 activity was assessed by fluorometric assay. In addition, mRNA expression levels of VGEF, vimentin, caspase-3, miRNA-145, Bax and Bcl-2 genes were quantified by real-time PCR. A scratch test was also performed to assess the effects of HCF on cell migration. The MTT assay revealed that the growth of H1299 cells increased when treated with 60 μg/mL of fertile HCF for 24 h. The fold change of caspase-3, miRNA-145, Bax/Bcl-2 ratio and caspase-3 activity was lower in HCF-treated H1299 cells compared to the control cell. The fold change in VGEF and vimentin gene expression was higher in the HCF-treated H1299 cells than in the control cell. The scratch test results showed that H1299 cell mobility increased 24 and 48 h after exposure to HCF. Our results suggest that the downregulation of miR-145 in HCF-treated H1299 cells may play a role as a possible oncogenic regulator of lung cancer growth. To confirm this assumption, further studies are required to evaluate the microRNA profile and effective oncogenes in vivo.

(S)-3-(3,4-Dihydroxybenzyl) piperazine-2,5-dione (cyclo-Gly-L-DOPA or CG-Nio-CGLD) peptide loaded in Chitosan Glutamate-Coated Niosomes as anti-Colorectal cancer activity

BackgroundColorectal cancer (CRC), now the second most prevalent malignant tumor worldwide, is more prevalent in young adults. In recent decades, there has been progress in creating anti-colorectal cancer medications, including cytotoxic compounds.ObjectivesNovel anticancer drugs are needed to surmount existing obstacles. A recent study investigated the effectiveness of novel formulations in preventing colorectal cancer.MethodsDuring this study, we assessed a new kind of niosome called cyclo-Gly-L-DOPA (CG-Nio-CGLD) made from chitosan glutamate. We evaluated the anti-colorectal cancer properties of CG-Nio-CGLD utilizing CCK-8, invasion assay, MTT assay, flow cytometry, and cell cycle analysis. The transcription of genes associated with apoptosis was analyzed using quantitative real-time PCR. At the same time, the cytotoxicity of nanomaterials on both cancer and normal cell lines was assessed using MTT assays. Novel anticancer drugs are needed to surmount existing obstacles. A recent study investigated the effectiveness of newly developed formulations in preventing colorectal cancer.ResultsThe Nio-CGLD and CG-Nio-CGLD were spherical mean diameters of 169.12 ± 1.87 and 179.26 ± 2.17 nm, respectively. Entrapment efficiency (EE%) measurements of the Nio-CGLD and CG-Nio-CGLD were 63.12 ± 0.51 and 76.43 ± 0.34%, respectively. In the CG-Nio-CGLD group, the percentages of early, late, necrotic, and viable CL40 cells were 341.93%, 23.27%, 9.32%, and 25.48%. The transcription of the genes PP53, cas3, and cas8 was noticeably higher in the treatment group compared to the control group (P > 0.001). Additionally, the treatment group had lower BCL2 and survivin gene expression levels than the control group (P < 0.01). Additionally, CG-Nio-CGLD formulations demonstrated a biocompatible nanoscale delivery mechanism and displayed little cytotoxicity toward the CCD 841 CoN reference cell line.ConclusionThese findings indicate that chitosan-based noisome encapsulation may enhance the effectiveness of CG-Nio-CGLD formulations in fighting cancer.

TREK-1 channel as a therapeutic target for dexmedetomidine-mediated neuroprotection in cerebral ischemia.

Our objective is to explore the protective effect of Dexmedetomidine on brain apoptosis and its mechanism through TREK-1 pathway. Forty male Sprague-Dawley rats were allocated into four groups: Sham, Cerebral Ischemia/Reperfusion Injury (CIRI), 50µg/kg Dex, and 100µg/kg Dex. A rat model of middle cerebral artery occlusion (MCAO) was employed to simulate cerebral embolism. Primary cortical neurons were exposed to Dex for 48h, with some receiving additional treatment with 100 µM yohimbine hydrochloride (YOH) or TREK-1 small interfering RNA (siRNA). Neuronal damage was assessed using hematoxylin and eosin (HE) staining. Cell viability and apoptosis were measured by Cell Counting Kit-8 (CCK8) and flow cytometry, respectively. Protein and gene expression levels of Bcl-2, Bax, and TREK-1 were determined by Western blot and real-time polymerase chain reaction (PCR). Histopathological changes revealed that Dex treatment at both 50µg/kg and 100µg/kg significantly mitigated neuronal damage compared to the CIRI group. YOH treatment and Trek1 siRNA significantly reduced cell viability (p < 0.05). The mRNA expression and protein levels of TREK-1 and Bax were remarkably increased, while mRNA expression and protein levels of Bcl-2 was seriously decreased after CIRI modeling. In contrast, Dex treatment at both concentrations led to decreased TREK-1 and Bax expression and increased Bcl-2 expression in primary cortical neurons. Addition of 100 µM YOH and Trek1 siRNA reversed the effects of Dex on apoptosis-related genes (p < 0.05). Dex exerts neuroprotective effects through the TREK-1 pathway in vivo and in vitro.

In-vitro study of cytotoxic and apoptotic potential of Thalassia hemprichii (Ehren.) Asch. And Enhalus acoroides (L.f.) Royle against human breast cancer cell line (MCF-7) with correlation to their chemical profile

BackgroundBreast cancer is the most common type of cancer diagnosed in women. Finding novel therapeutic agents with significant cytotoxic action and minimal adverse impact on normal cells becomes crucial. Today, natural anticancer agents present an unconventional method of treating cancer, either as a curative or preventative agent, with considerable concern for marine organisms.MethodsThe anticancer effect of the alcoholic extract of different Red Sea Seagrasses on MCF-7 human breast cancer cell line has been investigated. Seagrasses were collected from Wadi El Gamal, Red Sea and extracted. Qualitative HPLC analysis was performed on the extracts for the identification of their active biomarkers. This study was aimed to explore the cytotoxic impact of Thalassia hemprichii (Ehren.) and Enhalus acoroides (L.f.) Royle on MCF-7 and their mode of action. Their anti-proliferative effects on cancer cells were performed using Neutral red assay. On the other hand, their apoptotic effect and their capacity to induce cell cycle arrest were investigated by flow cytometry assay. The effect of Seagrasses on the mitochondrial membrane potential (ΔψM) was studied by using JC-1 mitochondrial membrane potential assay kit in Seagrasses treated cancer cells to Δψ Caspases 3/7activity was examined using the colorimetric method. Gene expression analysis and quantitative real time RT-PCR for the sea grasses on MCF-7 was performed. Immune-blotting technique for Bcl-2 and p53 was investigated.ResultsHPLC analysis demonstrated that the extracts contained mainly flavonoids and polyphenols such as Caffeic acid, Chlorogenic acids, catechin and kaempferol that might be responsible for these anticancer effects. Seagrasses alcoholic crude extract markedly suppressed the growth and expansion of MCF-7 cells concentration-dependently with no toxicity against normal human skin fibroblast HSF. Thalassia hemprichii and Enhalus acoroides trigger mode of cell death primarily via apoptosis as confirmed by the flow cytometry. Additionally, they have ability to induce G0/S cell cycle arrest in MCF-7. The data showed the depletion in mitochondrial membrane potential (ΔψM) in the treated cells dose-dependently Caspases 3/7activities markedly increased following 24 h treatment. Finally, Gene expression analysis showed a marked reduction in Bcl-2, Survivin and CDC2 gene expression levels and a significant increase in the expression of p53 and CC2D1A as compared to control cells.ConclusionIn summary, the Methanolic extract of seagrass, Thalassia hemperchii and Enhalus ocoroides are able to induce concentration-dependent cytotoxic effects in human MCF-7 cells through intrinsic pathway of apoptosis in MCF-7 cells. This study reveals the beneficial importance of sea grasses as a source of anticancer agents. Further in vivo study is recommended for the active isolated biomolecules.

Synergistic protective effects of 3,4-dihydroxyphenylglycol and hydroxytyrosol in male rats against induced heat stress-induced reproduction damage

Testicular heat stress disrupts spermiogenesis and damages testicular tissue. The study aims to assess 3,4-dihydroxyphenylglycol (DHPG) and hydroxytyrosol (HT) from olive oil as antioxidants to reduce heat-induced testicular damage. Seven groups of 35 male rats were used. Group I got normal saline. Group 2 had HS (43 °C for 20 min/day) and normal saline for 60 days. Groups 3–7 had HS and DHPG/HT doses (0.5 mg/kg DHPG, 1 mg/kg DHPG, 5 mg/kg HT, 0.5 mg/kg DHPG + 5 mg/kg HT, and 1 mg/kg DHPG + 5 mg/kg HT). The evaluation included tests on testicular tissue, sperm quality, oxidative status, gene activity, and fertility after 60 days. After DHPG and HT treatment, sperm motility, viability, and plasma membrane functionality, as well as levels of total antioxidant capacity (TAC), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT), and Bcl-2 gene expression, and in vivo fertility indexes increased. Meanwhile, abnormal morphology and DNA damage decreased, along with levels of glutathione (GSH), nitric oxide (NO), and malondialdehyde (MDA), and Bax, caspase-3, and caspase-9 gene expression, compared to the HS group. The study found that DHPG and HT have a more substantial synergistic effect when used together, improving reproductive health.

Investigating the Expression Levels of Bax and Bcl-2 Genes in Peripheral Blood Lymphocytes of Industrial Radiation Workers in the Asaluyeh Region.

Industrial radiography uses gamma or X-ray radionuclide sources to investigate the safety of industrial materials. Industrial radiation workers receive the highest occupational radiation doses. The present study investigates the relationship between Bax and Bcl-2 gene expression variables in industrial radiation workers. In this case-control study, data was collected using blood sampling from 40 workers, including two groups of non-radiation and radiation workers employed at the location. Expression levels of Bax and Bcl-2 genes were assessed in the laboratory. The environmental and absorbed doses of workers were measured using environmental and pen dosimeters. Statistical analysis showed that the radiation group's Bcl-2 gene expression level was significantly higher. Findings also demonstrated a correlation between Bcl-2 gene expression and the number of workdays. Also, the Bax gene expression did not show a significant change, and the expression ratio of Bax/Bcl-2 was insignificant in the two groups. Exposure to low doses of radiation could promote an adaptive response in cells by increasing Bcl-2 gene expression.

Alpha terpineol preconditioning enhances regenerative potential of mesenchymal stem cells in full thickness acid burn wounds

Regeneration of full thickness burn wounds is a significant clinical challenge. Direct stem cell transplantation at the wound site has a promising effect on wound regeneration. However, stem cell survival within the harsh wound environment is critically compromised. In this regard, preconditioning of stem cells with cytoprotective compounds can improve the efficiency of transplanted cells. This study evaluated the possible effect of alpha terpineol (αT) preconditioned mesenchymal stem cells (αT-MSCs) in full thickness acid burn wound. An optimized concentration of 10 μM αT was used for MSC preconditioning, followed by scratch assay analysis. A novel rat model of full thickness acid burn wound was developed and characterized via macroscopic and histological examinations. Treatment (normal and αT-MSCs) was given after 48 h of burn wound induction, and the healing pattern was examined till day 40. Skin tissues were harvested at the early (day 10) and late (day 40) wound healing phases and examined by histological grading, neovascularization, and gene expression profiling of healing mediators. In scratch assay, αT-MSCs exhibited enhanced cell migration and wound closure (scratch gap) compared to normal MSCs. In vivo findings revealed enhanced regeneration in the wound treated with αT-MSCs compared to normal MSCs and untreated control. Histology revealed enhanced collagen deposition with regenerated skin layers in normal MSC- and αT-MSC treated groups compared to the untreated control. These findings were correlated with enhanced expression of α-SMA as shown by immunohistochemistry. Additionally, αT-MSC group showed reduced inflammation and oxidative stress, and enhanced regeneration, as witnessed by a decrease in IL-1β, IL-6, TNF-α, and Bax and an increase in BCL-2, PRDX-4, GPX-7,SOD-1, VEGF, EGF, FGF, MMP-9, PDGF, and TGF-β gene expression levels at early and late phases, respectively. Overall findings demonstrated that αT exerts its therapeutic effect by mitigating excessive inflammation and oxidative stress while concurrently enhancing neovascularization. Thus, this study offers new perspectives on managing full thickness acid burn wounds in future clinical settings.

The protective role of selenium against high-fructose corn syrup–induced kidney damage: a histopathological and molecular analysis

With the growth of the food industry, fructose, the intake of which increases with food, causes obesity and metabolic syndrome. Kidney damage may develop from metabolic syndrome. Selenium (Se) participates in the structure of antioxidant enzymes and has a medicinal effect. In this work, the protective impact of Se on kidney damage produced by high-fructose corn syrup (HFCS) via endoplasmic reticulum (ER) stress was examined. The study comprised four groups, each consisting of ten experimental animals: control, HFCS (20%-HFCS), HFCS (20%-HFCS), + Se (0.3 mg/kg/day/po), and Se (0.3 mg/kg/day/po) alone. The duration of the experiment was 6 weeks. Kidney tissues were stained with hematoxylin and eosin for histological examination. Immunohistochemical analysis was conducted to assess TNF-α and caspase-3 levels. The spectrophotometric evaluation was performed to measure TOS (total oxidant status), TAS (total antioxidant status), and OSI (oxidative stress index) levels. The PERK, ATF4, CHOP, BCL-2, and caspase-9 gene expression levels were assessed by the RT-qPCR method. After Se treatment, histopathological abnormalities and TNF-α and caspase-3 levels in the HFCS+Se group decreased (p < 0.001). While TOS and OSI levels increased dramatically in the HFCS group, TAS values decreased significantly but improved after Se application (p < 0.001). The expression levels of the genes PERK, ATF4, CHOP, and caspase-9 were significantly lower in the HFCS group when compared to the HFCS+Se group (p < 0.05). Our findings suggest that Se may protect against ER stress, oxidative stress, apoptosis, and kidney damage caused by high-dose fructose consumption.

Neuropilin-1 Binding Peptide as Fusion to Diphtheria Toxin Induces Apoptosis in Non-small Cell Lung Cancer Cell Line.

Targeted cancer therapy can be considered as a new strategy to overcome the side effects of current cancer treatments. Neuropilin-1 (NRP-1) is a transmembrane glycoprotein that is expressed in endothelial cells and tumor vessels to stimulate angiogenesis progression. Targeted diphtheria toxin (DT)- based therapeutics are promising tools for cancer treatment. This study aimed to construct a novel NRP-1 binding peptide (as three repeats) (CRGDK) as a fusion to truncated DT (DTA) (DTA-triCRGDK) for targeted delivery of DT into NRP-1 expressing cells. The concept of DTA-triCRGDK was designed, synthesized and cloned into the bacterial host. Expression of DTA-triCRGDK was induced by Isopropyl ß-D-1-thiogalactopyranoside (IPTG) and purification was performed using Ni-NTA chromatography. Biological activity of DTA-triCRGDK was evaluated using MTT, apoptosis, and wound healing assays. In addition, expression levels of apoptotic Bax, Bcl2, and Casp3 genes were determined by Real-time PCR. Cytotoxicity analysis showed the IC50 values of DTA-triCRGDK for A549 and MRC5 were 0.43 nM and 4.12 nM after 24 h, respectively. Bcl2 expression levels decreased 0.4 and 0.72 fold in A549 and MRC5, respectively. However, Bax and Casp3 expression level increased by 6.75 and 8.19 in A549 and 2.51 and 3.6 in MRC5 cells. Taken together, DTA-triCRGDK is a promising tool for targeted therapy of NRP-1 overexpressing cancer cells.

The apoptotic effects of progesterone and testosterone on colon cancer (SW480) cells

Introduction: The association of sex steroids with cancer cell proliferation has been reported in recent studies; however, the findings are still controversial. The present study aimed to determine the cytotoxic effects of progesterone and testosterone on colon cancer (SW480) cells and to evaluate the expression levels of Bcl-2 and Bax genes in SW480 cells. Materials and Methods: The SW480 cell line was divided into a control group (untreated) and groups treated with 125, 250, 500, and 1000 μg/mL of testosterone and progesterone. Cell viability was quantified by the MTT assay. qRT-PCR was performed to evaluate gene expression levels. Flow cytometry was used to assess the apoptosis in cancer cells. Data were analyzed using the student's t-test and ANOVA. Results: The expression level of the Bax gene significantly decreased in SW480 cells exposed to a cytotoxic dose of progesterone. Moreover, the expression level of the Bax gene significantly increased in the SW480 cells exposed to a cytotoxic dose of testosterone. Conclusion: The results of the present study showed that testosterone might affect the apoptosis of colon cancer cells at low concentrations. Studies have shown that progesterone can induce tumor cell death in cancer cells. Accordingly, the clinical use of testosterone and progesterone therapy for cancer treatment is highly controversial.