Expression Of Anti-apoptotic Genes Research Articles

Partial Inhibition of Epithelial-to-Mesenchymal Transition (EMT) Phenotypes by Placenta-Derived DBMSCs in Human Breast Cancer Cell Lines, In Vitro.

Stem cell-based therapies hold significant potential for cancer treatment due to their unique properties, including migration toward tumor niche, secretion of bioactive molecules, and immunosuppression. Mesenchymal stem cells (MSCs) from adult tissues can inhibit tumor progression, angiogenesis, and apoptosis of cancer cells. We have previously reported the isolation and characterization of placenta-derived decidua basalis mesenchymal stem cells (DBMSCs), which demonstrated higher levels of pro-migratory and anti-apoptotic genes, indicating potential anti-cancer effects. In this study, we analyzed the anti-cancer effects of DBMSCs on human breast cancer cell lines MDA231 and MCF7, with MCF 10A used as control. We also investigated how these cancer cells lines affect the functional competence of DBMSCs. By co-culturing DBMSCs with cancer cells, we analyzed changes in functions of both cell types, as well as alterations in their genomic and proteomic profile. Our results showed that treatment with DBMSCs significantly reduced the functionality of MDA231 and MCF7 cells, while MCF 10A cells remained unaffected. DBMSC treatment decreased epithelial-to-mesenchymal transition (EMT)-related protein levels in MDA231 cells and modulated expression of other cancer-related genes in MDA231 and MCF7 cells. Although cancer cells reduced DBMSC proliferation, they increased their expression of anti-apoptotic genes. These findings suggest that DBMSCs can inhibit EMT-related proteins and reduce the invasive characteristics of MDA231 and MCF7 breast cancer cells, highlighting their potential as candidates for cell-based cancer therapies.

Hyperthermia Potentiates the Effectiveness of Anticancer Drugs-Cisplatin and Tamoxifen on Ovarian Cancer Cells In Vitro.

Ovarian cancer is one of the most prevalent cancers among women. Due to the frequent problems during treatment, such as relapses or the development of resistance to treatment, new methods of treating this disease are being sought. A special attention is directed towards the combination therapies combining several different anticancer agents. The aim of the following study was to examine the effect of combination therapy with mild hyperthermia (temperatures of 39 °C and 40 °C) and anticancer drugs-cisplatin and tamoxifen-on the SKOV-3 ovarian cancer cell line in vitro. Furthermore, the study also assessed the effect of moderate hyperthermia on the anticancer effectiveness of both of these drugs. The cytotoxic effect of the therapy was assessed using MTT assay and fluorescent acridine orange staining. Changes in the expression of genes involved in apoptosis processes were evaluated using RT-qPCR. It has been shown that the use of combination therapy leads to a significant increase in apoptosis processes in SKOV-3 ovarian cancer cells and, consequently, to a decrease in their viability. At the molecular level, mild hyperthermia leads primarily to a decrease in the expression of anti-apoptotic genes, and also, to a small extent, to an increase in the expression of proapoptotic genes. The results also indicate that moderate hyperthermia has a positive effect on the cytotoxic efficacy of both cisplatin and tamoxifen on ovarian cancer cells. This suggests that hyperthermia could be a potential component in combination therapy for ovarian cancer.

Synthesis, DPPH Radical Scavenging, Cytotoxic Activity, and Apoptosis Induction Efficacy of Novel Thiazoles and Bis-thiazoles.

Heterocyclic materials-containing thiazoles exhibited incredible importance in pharmaceutical chemistry and drug design due to their extensive biological properties. Synthesis of thiazoles and bis-thiazoles from the reaction of 2-((6-Nitrobenzo[ d][1,3]dioxol-5-yl)methylene)hydrazine-1-carbothioamide with hydrazonoyl chlorides in dioxane and in the existence of triethylamine as basic catalyst. The antioxidant, in vitro antiproliferative, and cytotoxicity efficacy of thiazoles and bis-thiazoles were measured. In this work, novel series of 5-methyl-2-(2-(-(6-nitrobenzo[d][1,3]dioxol-5-yl)methylene) hydrazinyl)-4-(aryldiazenyl)thiazoles (4a-f) were prepared via the reaction of hydrazonoyl chlorides 2a-f with 2-((6-nitrobenzo[d][1,3]dioxol-5-yl)methylene)hydrazine-1-carbothioamide (1) in dioxane and employing triethylamine as basic catalyst. Following the same procedure, bisthiazoles (6, 8, and 10) have been synthesized by utilizing bis-hydrazonoyl chlorides (5, 7, and 9) and carbothioamide 1 in a molar ratio (1:2), respectively. The distinctive features in the structure of isolated products were elucidated by spectroscopic tools and elemental analyses. The antioxidant, in vitro anti-proliferative, cytotoxicity, and anti-cancer efficacy of thiazoles and bis-thiazoles were evaluated. Compounds 4d and 4f were the most potent antioxidant agents. Gene expression of apoptosis markers and fragmentation assay of DNA were assessed to explore the biochemical mechanism of synthesized products. Thiazoles significantly inhibited cell growth and proliferation more than bis-thiazoles. They induced apoptosis through induction of apoptotic gene expression P53 and downregulation of antiapoptotic gene expression Bcl-2. Moreover, they induced fragmentation of DNA in cancer cells, indicating that they could be employed as anticancer agents by inhibiting tumor growth and progression and can be considered effective compounds in the strategy of anti-cancer agents' discovery. Synthesis, DPPH Radical Scavenging, Cytotoxic activity, and Apoptosis Induction Efficacy based on Novel Thiazoles and Bis-thiazoles.

SPINK13 acts as a tumor suppressor in hepatocellular carcinoma by inhibiting Akt phosphorylation

The PI3K/Akt pathway is overexpressed in nearly 50% of hepatocellular carcinomas and inhibits apoptosis by promoting the expression of antiapoptotic genes. Serine protease inhibitors have been shown to induce apoptosis in hepatoma cells by downregulating SPINK13 in the PI3K/Akt pathway. In this study, SPINK13 was expressed in lentiviral vectors. Changes in signaling pathway adapter proteins, apoptosis regulatory proteins, cell cycle regulatory proteins, and the biological behavior of hepatocellular carcinoma were observed in cell and nude mouse xenograft models. The underlying mechanism of endogenous SPINK13-induced apoptosis in hepatocellular carcinoma cells was explored via transcriptomics. As a result, endogenous SPINK13 might inhibit the activity of Furin protease, downregulate the Notch1/Hes1 pathway in a binding manner, activate the direct effector PTEN, inhibit Akt phosphorylation, inactivate the downstream PI3K/Akt pathway, and ultimately lead to mitochondrial apoptosis and cell cycle arrest in hepatoma cells. Therefore, the Notch1/Hes1/PTEN pathway may act upstream of SPINK13 to downregulate the PI3K/Akt signaling pathway. Our study helps elucidate the underlying mechanism of SPINK13 in anti-hepatocellular carcinoma and lays a theoretical foundation for the development of novel therapeutic serine protease inhibitors.

Systemic Inflammation Decreases Initial Brain Injury but Attenuates Neurite Extension and Synapse Formation during the Repair of Injured Brains.

In this study, we explored the impact of systemic inflammation on initial brain injury and repair processes, including neurite extension and synapse formation. For this purpose, we established a brain injury model by administering adenosine triphosphate (ATP), a component of damage-associated molecular patterns (DAMPs), through stereotaxic injection into the striatum of mice. Systemic inflammation was induced by intraperitoneal injection of lipopolysaccharide (LPS-ip). Bulk RNA-sequencing (RNA-seq) analyses and immunostaining for microtubule-associated protein 2 (MAP2) and tyrosine hydroxylase (TH) showed that LPS-ip led to a reduction in initial brain injury, but inhibited neurite extension into the damaged brain. LPS-ip upregulated expression of defense response genes and anti-apoptotic genes, but decreased expression of genes associated with repair and regeneration. In addition, LPS-ip reduced levels of vGlut1 and PSD95 (markers for excitatory pre and post synapses, respectively), but had little effect on vGAT and gephyrin (markers for inhibitory pre and post synapses, respectively). Taken together, these findings suggest that systemic inflammation reduce initial damage but impede subsequent repair process.

Enhancing sensitivity to oxaliplatin in tongue squamous cell carcinoma: mechanistic insights and therapeutic potential of DHA combination therapy.

Squamous cell carcinoma of the tongue, a common and aggressive malignancy, poses a substantial threat to health and well-being. Despite the promising results of combination therapy with dihydroartemisinin (DHA) and oxaliplatin (Oxa) in various cancers, its effectiveness in treating tongue squamous cell carcinoma had not been explored prior to this study. Our research found that DHA significantly enhances the sensitivity of tongue squamous cell carcinoma cells to Oxa, even at very low concentrations. The combination treatment was observed to modulate the activity of CDK1 and Cyclin B1, arresting the cell cycle in the G2 phase. Additionally, it reduces mitochondrial membrane potential, prompting the release of cytochrome c and activating cleaved caspase-3, which promotes apoptosis. Notably, surface plasmon resonance and immunoprecipitation experiments revealed that DHA targets and attenuates CDK1 modification, weakening its interaction with STAT3 protein. This leads to reduced expression of anti-apoptotic genes and facilitates programmed cell death in CAL-27 cells. The findings underscore the potential of DHA and Oxa as a potent therapeutic strategy for tongue squamous cell carcinoma, opening avenues for clinical application and further exploration into its mechanistic pathways.

Long non-coding RNA PANDA promotes endothelial senescence and oxidative damage through the interaction with NRF2

Abstract Background Accumulation of reactive oxygen species and inflammation are major features of diabetic vasculopathy, yet the underlying mechanisms remain elusive. LncRNAs are emerging as important players in the pathogenesis of cardiovascular disease. PANDA, a newly identified lncRNA, is a key regulator of cellular senescence, apoptosis and oxidative stress. Purpose To investigate the role and molecular mechanism of PANDA in diabetic vascular disease. Methods RNAseq was performed to aorta specimen from diabetic and no diabetic patients as well to HAECs exposed to 5 mM and 25 mM concentrations (Normal -NG- and High -HG-, respectively). PANDA depletion in HG-treated HAECs was obtained by siRNA transfection while a scrambled siRNA wass used as a negative control. RNAseq and network perturbation analysis (NPA) of treated HAECs unveiled transcriptional changes upon PANDA depletion. Expression of PANDA was assessed by real time PCR. PANDA RNA-IP was performed to check its binding to relevant transcriptional factor (such as NRF2) as well Ch-IP was performed to check the NRF2 binding on oxidative gene promoters. Cellular localization of NRF2 was investigated by Immunofluorescence. Beta-galactosidase and superoxide staining was used to detect endothelial senescence and ROS formation; while, migration and tube formation were employed to evaluate angiogenic properties of HAECs. Results PANDA expression was significantly increased in diabetic human aorta as well in HG-treated HAECs (Figure1 A-B). Transcriptomic analysis revealed dysregulation of several genes upon PANDA silencing with the antioxidant gene heme oxygenase-1 (HMOX1) as the top-ranking transcript in HG cells (Figure1 C-D). Western blot analysis reveals the restored level of HMOX1 and TFRC1 upon PANDA depletion (Figure1 E-G). NPA analysis showed a strong involvement of PANDA in senescence, DNA damage, NRF2 signaling, hypoxic stress response and proliferation. In HG, NFR2 is downregulated while PANDA silencing restores its level (Figure1 I-J). We found that in HG condition PANDA binds the transcription factor NRF2 and blocks its nuclear translocation thus impeding its binding on HMOX1 and TFRC promoters (Figure1 K-M). Silencing of PANDA in HG-treated HAECs reduced genes and cellular features of senescence (Figure2 A-B), restored the expression of anti-apoptotic genes and decreases caspase 3 activity (Figure2 C-D), improved endothelial migration and tube formation (Figure2 E and G), and reduced ROS formation (Figure2 F). Conclusions In hyperglycemia PANDA upregulation drives endothelial senescence while impairing angiogenic properties. On the other hand, PANDA depletion in HG-treated HAECs rescues maladaptive transcriptional changes through the release of NRF2 that in turn translocate into the nucleus enhancing the expression of the antioxidant gene HMOX1. The results indicate PANDA as a putative novel molecular target in the setting of diabetic vascular disease (Figure2 H).

Noradrenaline Protects Human Microglial Cells (HMC3) Against Apoptosis and DNA Damage Induced by LPS and Aβ1-42 Aggregates In Vitro.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, characterized by the accumulation of amyloid-beta (Aβ) plaques and neuroinflammation. This study investigates the protective effects of noradrenaline (NA) on human microglial cells exposed to lipopolysaccharides (LPS) and Aβ aggregates-major contributors to inflammation and cellular damage in AD. The reduced Aβ aggregation in the HMC3 human microglial cells co-treated with Aβ and NA was confirmed by thioflavin T (ThT) assay, fluorescent ThT staining, and immunocytochemistry (ICC). The significantly increased viability of HMC3 cells after 48 h of incubation with NA at 50 µM, 25 µM, and 10 µM, exposed to IC50 LPS and IC50 Aβ, was confirmed by XTT and LDH assays. Moreover, we found that NA treatment at 25 μM and 50 μM concentrations in HMC3 cells exposed to IC50 LPS or IC50 Aβ results in an increased proliferation of HMC3 cells, their return to normal morphology, decreased levels of DNA damage, reduced caspase-3 activity, decreased expression of pro-apoptotic DDIT3 and BAX, and increased expression of anti-apoptotic BCL-2 genes and proteins, leading to enhanced cell survival, when compared to that of the HMC3 cells treated only with IC50 LPS or IC50 Aβ. Furthermore, we showed that NA induces the degradation of both extracellular and intracellular Aβ deposits and downregulates hypoxia-inducible factor 1α (HIF-1α), which is linked to impaired Aβ clearance and AD progression. These findings indicate that NA holds promise as a therapeutic target to address microglial dysfunction and potentially slow the progression of AD. Its neuroprotective effects, particularly in reducing inflammation and regulating microglial activity, warrant further investigation into its broader role in mitigating neuroinflammation and preserving microglial function in AD.

CREBRF regulates apoptosis and estradiol via ISG15/ISGylation in pig granulosa cells

Granulosa cells play a crucial role in the reproductive processes of female animals, as their proliferation, apoptosis, and hormonal secretion are vital for follicular development and ovulation. Although the role and mechanisms of CREBRF in the reproductive system have been partly reported, its functions in ovarian granulosa cells have not been fully explored. In this study, the results indicated that the expression of CREBRF in the ovaries at 30 days after birth was significantly higher than that during puberty and sexual maturity. Studies on the function of CREBRF found that CREBRF could enhance the synthesis of estradiol and had no effect on progesterone synthesis in pig granulosa cells. At the same time, CREBRF could suppress apoptosis through the Bax/caspase3/caspase9 pathway and modulation of ISG15/ISGylation in pig granulosa cells. During this process, the expression of many genes changed in granulosa cells. Several genes (CMPK2, MX1, MX2, ZBP1, PML, CHAC1, and BAX) which were promoted apoptosis, were upregulated after CREBRF knockdown with siRNA. ISG15-protein conjugation genes (HERC5, UBA7, UBE2L6, ISG15) were also were upregulated. On the contrary, the expression of anti-apoptotic (RFK, SNAP23) genes decreased. In conclusion, CREBRF could enhance the synthesis of estradiol and acted as anti-apoptosis role in pig granulosa cells. This discovery can provide novel insights for further elucidating the molecular mechanisms of granulosa cells in the ovary and potentially identifies CREBRF as a molecular target for improving fertility.

Very early remission and increased apoptosis with the use of Pentoxifylline in children with acute lymphoblastic leukemia.

Despite the improvement in survival in acute lymphoblastic leukemia (ALL), there are still cases with evasion of chemotherapy-induced apoptosis. The IKK/NF-κB signaling pathway contributes to antiapoptotic gene expression. Pentoxifylline (PTX) inhibits IkB phosphorylation, blocking NF-κB and antiapoptotic activity. We conducted a randomized, double-blind clinical trial on pediatric ALL patients undergoing induction therapy, assigning them to PTX or placebo group. Bone marrow aspirates were obtained on days 1, 8, 15, and 22. Apoptosis was assessed using Annexin-V/propidium iodide. Results indicated that the PTX group exhibited higher apoptosis on day-8 (41.3% vs. 19.4%, p =0.029) and day-15 (35.0% vs. 14.2%, p <0.01). On day-8, the PTX group displayed an MRD of 0.25% vs. 18.2% (p <0.01) in placebo group; on day-15, the PTX group demonstrated an MRD of 0.09% vs. 1.4% (p =0.02). Patients achieving an MRD <0.01% on day-8 demonstrated a 3-year Overall Survival (OS) of 81.6% vs. 58.3% (p =0.03); on day-15, patients with MRD <0.01% had a 3-year OS of 77.9% vs. 54.5% (p =0.03). The PTX group achieved an MRD of <0.01% earlier on days-8 and 15, along with a higher apoptosis rate, indicating a more favorable therapeutic response. In the entire cohort, patients achieving MRD <0.01% on day-8 or 15 displayed superior OS. Our study demonstrates that PTX enhances apoptosis and reduces MRD in pediatric acute lymphoblastic leukemia patients. https://clinicaltrials.gov/, identifier NCT02451774.

Expression of Anti- Apoptotic Gene ( BARF1) and Immunomodulatory Gene (BCRF1) For Epstein Barr Virus in Chronic Active EBV Patients

Epstein Barr virus (EBV) is a herpes virus with double-stranded DNA enclosed by proteins. The envelope of the virus has glycoproteins, which are important for attachment and entry into the host cells (B cells and epithelial cells). EBV targets B cells by utilizing their molecular machinery to replicate the viral genome. The virus causes B cells to differentiate into memory B cells, which then can move into the circulatory system, or become latent until a trigger causes reactivation. The transmission of the Epstein Barr virus occurs in several ways, such as deep kissing or food-sharing. Increased levels of viral DNA are found in salivary secretions after the initial infection. Children can be infected after eating food that has already been chewed by an EBV infected individual. The transmission has occurred through stem cell and organ transplantation, as well as blood transfusion. EBV has several associated complications, One dangerous complication is splenic rupture due to infectious mononucleosis. Aim of the Study: To Estimation the immunemodulatory and Oncogenes for Epstein Barr Virus Associated with Viral Tumorigenesis in Chronic Active EBV Patients By Detection of EBV IgG in all samples , Estimation the expression of antiapoptotic gene ( BARF1) and immunomodulatory gene (BCRF1). Result: The study showed there are high significant between the patient group with different inflammation disease in addition infected with virus compare with have not disease When detection genetically about the virus in sample of infected by EBV the presence of genes has been diagnosed BARF1 and BCRF1 in patient's group.

Pre-Clinical Study of Hydro-Ethanol (60:40) Extract of &lt;i&gt;Areca catechu&lt;/i&gt; (L.) on Testicular Androgenesis in Albino Rat: An Approach for Herbal Male Contraceptive Development

The present study was designed to determine the anti-testicular activity of hydro-ethanol seed extract of Areca catechu (10, 20 and 40 mg) in dose-dependent fashion in albino rats. Seminal vesicular fructose (SVF), oxidative stress sensors, gene expression, somatic weight, reproductive organo-somatic indices, spermiological, hormonal profile, and testicular histological examination for qualitative and quantitative investigations of spermatogenesis were observed. In compared to the placebo treated control (PTC), the exposure of the said doses showed a statistical significant downward deviation in the spermiological, hormonal, SVF profile, kinetics of testicular key androgenic dehydrogenase enzymes, and diameters of seminiferous tubules. Anti-oxidant enzyme kinetics were reduced significantly against PTC, and the quantity of malondialdehyde in male gonad and sperm precipitate was elevated in significant level (p&lt;0.05). Expression of apoptotic promoting gene in testis was increased (p&lt;0.05) and anti-apoptotic Bcl-2 gene expression exhibited a significant decrease (p&lt;0.05) in treated group comparison to the PTC. The alterations in the activities of phosphatases in hepatic tissue was not significant from the background of PTC suggesting that the plant has no systematic undesirable effect in physiological processes. The observation highlighted that 10 mg dose as the threshold dose for imposition of such anti- testicular activity leading to male contraception.

Positive impact of indicaxanthin from Opuntia ficus-indica fruit on high-fat diet-induced neuronal damage and gut microbiota dysbiosis.

Indicaxanthin is a betalain that is abundant in Opuntia ficus-indica orange fruit and has antioxidative and anti-inflammatory effects. Nevertheless, very little is known about the neuroprotective potential of indicaxanthin. This study investigated the impact of indicaxanthin on neuronal damage and gut microbiota dysbiosis induced by a high-fat diet in mice. The mice were divided into three groups according to different diets: the negative control group was fed a standard diet; the high-fat diet group was fed a high-fat diet; and the high-fat diet + indicaxanthin group was fed a high-fat diet and received indicaxanthin orally (0.86 mg/kg per day) for 4 weeks. Brain apoptosis, redox status, inflammation, and the gut microbiota composition were compared among the different animal groups. The results demonstrated that indicaxanthin treatment reduced neuronal apoptosis by downregulating the expression of proapoptotic genes and increasing the expression of antiapoptotic genes. Indicaxanthin also markedly decreased the expression of neuroinflammatory proteins and genes and inhibited high-fat diet-induced neuronal oxidative stress by reducing reactive oxygen and nitrogen species, malondialdehyde, and nitric oxide levels. In addition, indicaxanthin treatment improved the microflora composition by increasing the abundance of healthy bacterial genera, known as producers of short-chain fatty acids (Lachnospiraceae, Alloprovetella, and Lactobacillus), and by reducing bacteria related to unhealthy profiles (Blautia, Faecalibaculum, Romboutsia and Bilophila). In conclusion, indicaxanthin has a positive effect on high-fat diet-induced neuronal damage and on the gut microbiota composition in obese mice.

Increasing prostate cancer radiosensitivity by miR-7-5p knockdown of anti-apoptotic genes

Despite the success of radiotherapy for prostate cancer treatment, the recent discovery of radiation resistance prevents it from reaching its full potential. This study aims to use hsa-miR-7-5p for the expression of anti-apoptotic genes. The search for anti-apoptotic genes was carried out through databases. The selected genes included XIAP, MCL1, REL, and BIRC3. Our selection was based on the best miRNA because it has a greater impact on genes. The second step involved transfecting the miRNA into a prostate cancer cell line. Subsequently, radiosensitivity was tested using real-time PCR, clonogenic assay, and annexin V flow cytometry. The highest apoptosis rate in the transfected cells was at 0 Gy in hsa-miR-7-5p (28.88 ± 0.80), plenti III (18.81 ± 0.59), and the control group (4.10 ± 1.52) (P<0.001). Also, its rate was at 4 Gy in hsa-miR-7-5p (36.11 ± 1.93), plenti III (26.42 ± 0.42), and the control group (8.79 ± 2.29) (P<0.001). This study showed a decreasing trend in survival with increasing doses. Suppression of anti-apoptotic genes, including XIAP, MCL1, Birc3, and REL, enhanced radiosensitivity by increasing the expression of hsa-miR-7-5p in the PC3 and LNCaP cell lines. Hsa-miR-7-5p is a miRNA that can suppress the expression of anti-apoptotic genes and thus plays an essential role in the process of cell apoptosis. Targeting genes that are associated with apoptosis could potentially enhance the efficacy of treatments for patients with prostate cancer.

The Effect of Resveratrol on Gamma Globin Gene Expression in Patients with Beta Thalassemia: The Role of Adaptation to Cellular Stress

HbF induction is an appropriate strategy to ameliorate the severity of β-thalassemia symptoms. Hydroxyurea (HU) is the most common chemical agent introduced as an HbF inducer but responsiveness to HU is variable and the introduction of HbF inducers alternative to HU with low cytotoxicity has been a crucial challenge. Resveratrol is an HbF inducer agent that may have favorable effects on the differentiation of hematopoietic erythroid progenitors (HEPs). The present study aimed to investigate the effect of resveratrol on γ-globin, stress response, and anti-apoptotic gene expression among hydroxyurea (HU)-responders and HU-nonresponders (HU-NR). Four cases of HU-R and four cases of HU-NR were studied. HEPs of the patients were cultured, and the expression of γ-globin, Foxo3, and Bclxl was assessed. Moreover, the differentiation and apoptotic rate of the cells were investigated using flow cytometry analysis. In three cases, the γ-globin gene expression increased after resveratrol treatment. All of the HU-NR patients were also non-responders to resveratrol (Res-NR). The expression of Foxo3 and Bclxl genes was higher in responders to resveratrol (Res-R) compared to non-responders (Res-NR). The rate of apoptosis in Res-R patients was also lower than in Res-NR. Responders to resveratrol also had a higher rate of HEP maturation. The cells of both HU–NR and Res-NR patients could not adapt to stress conditions and proceed to the erythroid differentiation. In conclusion, resveratrol increased the γ-globin expression in HEPs of β-thalassemia patients. The response was observed only in R-HU patients with similar cellular pathways.

Development of mesoporous magnetic nanoparticles supported idarubicin and investigation of apoptotic and cytotoxic effects on cancer cell lines.

Many methods are used for cancer treatment, especially chemotherapy. In addition to the their therapeutic effects, chemotherapeutic drugs also have serious disadvantages, such as not being cell and tissue-specific, causing toxicity in many tissues, and developing drug resistance. Many methods, especially nanocarriers, have been designed to overcome these disadvantages. In this study, we synthesized mesoporous silica iron oxide nanoparticles with different pore diameters and loaded idarubicin (6MFe3O4-NH2-IDA and 35MFe3O4-NH2-IDA). The synthesized molecules were characterized using FT-IR, XRD, and SEM methods. The cytotoxic effects of unbound idarubicin and idarubicin-loaded nanoparticles on MCF7 and HL-60 cell lines were examined by MTT test. Additionally, the expression of anti-apoptotic (Survivin and BCL-2) and apoptotic (BAX, PUMA, and NOXA) genes of the nanoparticles were measured by PCR method. As a result of the analyses, it was seen that nanoparticles with the desired properties and sizes were synthesized. In MTT analysis, it was observed that both nanoparticles dramatically decreased the IC50 value in cell lines. However, the 35MFe3O4-NH2-IDA molecule was found to have lower IC50 values. IC50 values ​​for pristine IDA, 6MFe3O4-NH2, and 35MFe3O4-NH2 at 24h were found to be 3.56, 1.24 and 0.25 µM in the MCF7 cell line and 4.15, 1.16 and 0.34 µM in the HL-60 cell line, respectively. Additionally, apoptotic gene expression increased, and anti-apoptotic gene expression decreased. Our study demonstrates that the effectiveness of idarubicin can be significantly enhanced by its application with mesoporous nanocarriers. This enhancement is attributed to the controlled release of idarubicin from the nanocarrier, which circumvents drug resistance mechanisms, improves drug solubility, and increases the drug-carrying capacity per unit volume due to the porous structure of the carrier. These findings underscore the potential of the synthesized nanocarrier in cancer treatment and provide a clear direction for future research in this field.

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.

Preventive Effect of Alpha-pinene on Cisplatin-induced Kidney Injury by Oxidative Stress, Inflammation and Apoptosis via NF-κB Signaling Pathway

Introduction: The chemotherapy medication cisplatin is highly effective and is used in treating a wide variety of cancers. Tumor resistance and dose-related severe side effects, including kidney and hearing damage and suppressed bone marrow function, limit its clinical utility. This study aimed to investigate the nephroprotective effect of alpha-pinene against cisplatin-induced nephrotoxicity in male albino Wistar rats. Methods: A total of 24 rats were divided into four groups containing six animals. Alpha-pinene (50 mg/kg) was administered orally for 14 days, and cisplatin (50 mg/kg) was given intraperitoneally for the last two consecutive days (13th and 14th day). Kidney function markers, lipid peroxidative markers, antioxidant status, inflammatory markers, and apoptotic gene expressions were analyzed. The cisplatin-induced rats significantly elevated kidney function markers, inflammatory markers, and pro-apoptotic genes in kidney tissues. Further, the antioxidant level/activities and antiapoptotic gene expression were significantly diminished in cisplatin-induced rats. Results: Pretreatment with alpha-pinene significantly decreased kidney function markers, inflammatory markers, and pro-apoptotic genes and increased antioxidant status and antiapoptotic genes. Conclusion: These findings provide the protective effect of alpha-pinene against CP-induced nephrotoxicity, as measured by potent antioxidant and antiapoptotic properties.

Reduced aggregation of the leghorn male hepatoma cell line in suspension by supplementing dextran sulfate in the media.

The study aimed to improve the efficiency of leghorn male hepatoma (LMH) cells for animal virus vaccine production by transitioning from adherent to suspension culture and evaluating the effects of dextran sulfate (DS) on preventing cell aggregation. The goal was to enhance cell growth, viability, and glucose metabolism and to develop efficient suspension-adapted LMH cells for large-scale vaccine production. LMH cells previously cultured in an adherent state were transferred to 125 mL Erlenmeyer flasks to conduct suspension culture. Cell culture performance, including cell density, viability, and glucose metabolism, during the cultures was measured, along with an assessment of cell aggregation. Additionally, mRNA expression levels of genes associated with cell adhesion and apoptosis were monitored. DS supplementation in suspension culture enhanced cell viability and growth, with higher cell densities and viabilities compared to control media. Additionally, DS supplementation reduced glucose consumption and waste production, indicating improved metabolic efficiency. DS also delayed cell aggregation, possibly by downregulating integrin expression and promoting anti-apoptotic gene expression. However, even after 2 months, cell aggregation persisted in both control and DS-supplemented cultures, suggesting further optimization is needed for LMH cell adaptation to suspension culture. DS supplementation in LMH cell suspension cultures led to notable improvements in cell growth, viability, and glucose metabolism, while also decreasing the cell aggregation.

Lambda-cyhalothrin induces heart injury in chickens by regulating cytochrome P450 enzyme system and inhibiting Nrf2/HO-1 pathway

Lambda-cyhalothrin (LCT) is a common pyrethroid insecticide widely used for ectoparasite control and hygiene pest prevention in poultry and this study aimed to investigate the mechanisms of LCT-induced cardiac injury in chickens. Low, medium, and high-dose LCT exposure models in chickens were established and hematoxylin and eosin (H&E) staining, dihydroethidium (DHE) staining, TUNEL staining, immunofluorescence, biochemical analysis, and gene expression analysis were used to study the effects of LCT exposure on the chicken heart. The results showed that LCT exposure increased the serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH), led to muscle fiber breakage and inflammatory cell infiltration and caused cardiac tissue damage. The DHE staining and biochemical analysis revealed that LCT exposure resulted in the excessive accumulation of ROS, decreased activities/levels of catalase (CAT), total superoxide dismutase (T-SOD), and glutathione (GSH), and increased levels of the oxidative damage marker malondialdehyde (MDA). The TUNEL staining indicated that LCT exposure increased apoptosis possibly through the elevated expression of pro-apoptotic genes in the mitochondrial pathway, the reduced expression of anti-apoptotic genes, the upregulation of pro-inflammatory factors and the downregulation of anti-inflammatory factors. Here, LCT exposure significantly inhibited the expression of genes in the Nrf2/HO-1 pathway and activated the expression of genes in the CYP450 enzyme system. Compared to the low-dose group, the high-dose LCT exposure group showed lower levels of apoptosis and inflammation, possibly related to the low oxidative stress levels mediated by the decreased expression of the CYP450 enzyme system. In conclusion, LCT exposure induces oxidative stress, apoptosis, and inflammation in chicken hearts, which may be associated with the inhibition of the Nrf2/HO-1 pathway and activation of the CYP450 enzyme system. This study provides a theoretical basis for the safer use of insecticides in poultry production.