CASP8 Genes Research Articles

In vitro immune-depression and anti-inflammatory activities of cantharidin on gilthead seabream (Sparus aurata) leucocytes activated by λ-carrageenan

Cantharidin is a natural compound with known therapeutic applications in humans. The aim of this study was to investigate the in vitro effects of cantharidin on gilthead seabream (Sparus aurata) head kidney leucocytes (HKL) stimulated with λ-carrageenan. HKLs were incubated for 24 h with cantharidin (0, 2.5 and 5 μg mL−1) and λ-carrageenan (0 and 1000 μg mL−1). The results showed that HKL viability only decreased by 15.2% after incubated with 5 μg mL−1 of cantharidin and λ-carrageenan. Cantharidin increased the peroxidase activity of HKLs only when incubated in combination with λ-carrageenan. Besides this, cantharidin inhibited the respiratory burst and phagocytic activities. Furthermore, cantharidin induced morphological changes in HKLs (apoptotic and vacuolization signs) that were enhanced when incubated with λ-carrageenan. Considering the analysis of the selected gene expression studied in HKLs [NF-κB subunits (rela, relb, crel, nfkb1, nfkb2), proinflammatory cytokines (il1b, tnfa), anti-inflammatory cytokines (il10, tgfb) and caspases (casp1, casp3, casp8, casp9)], although λ-carrageenan up-regulated the expression of the proinflammatory gene il1b, λ-carrageenan and cantharidin down-regulated its expression in HKLs. In addition, cantharidin up-regulated casp3 and casp9 expression. The casp3 and casp9 gene expression was down-regulated while casp1 gene expression was up-regulated in HKLs incubated with both cantharidin and λ-carrageenan. All the effects of cantharidin are related to its inhibitory effect on protein phosphatases, which induce apoptosis at long exposure times, and minimize the effects of λ-carrageenan. The present results provide detailed insight into the immune-depressive and anti-inflammatory properties of cantharidin on immune cells, which could be of interest to the aquaculture sector.

Evaluation of the Cytotoxic Effect of Cobalt Oxide Nanoparticles Functionalized by Glucose and Conjugated with Lapatinib (Co3O4@Glu-Lapatinib) on a Lung Cancer Cell Line and Evaluation of the Expression of CASP8, mTOR1, and MAPK1 Genes

Evaluation of the Cytotoxic Effect of Cobalt Oxide Nanoparticles Functionalized by Glucose and Conjugated with Lapatinib (Co3O4@Glu-Lapatinib) on a Lung Cancer Cell Line and Evaluation of the Expression of CASP8, mTOR1, and MAPK1 Genes

Pharmacological Mechanisms of Periplocae Cortex Against Congestive Heart Failure Based on Network Pharmacology and Experimental Evaluation

Background Periplocae cortex is a well-known Traditional Chinese Medicine with abundant effects, including the treatment of chronic congestive heart failure (CHF). However, the principal components and mechanisms have not been fully elucidated. This study aims to analyze the active ingredients and potential mechanisms of the periplocae cortex in CHF treatment. Methods TCMSP, GeneCards, and Comparative Toxicogenomics databases were used to mine the active ingredients and potential targets of the periplocae cortex. Cytoscape 3.9.1 software was employed to construct the “periplocae cortex-active ingredients-potential targets” and protein–protein interaction network. The DAVID 6.8 database was used for Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the predicted targets. The protective effects of β-sitosterol (BSS) were detected in doxorubicin (Dox)-induced H9c2 cells using MTT assay, while the regulatory pathways of BSS were examined using various assays, including real-time quantitative PCR and Western blot. The cardiac troponin I (cTn-I) concentration was also measured. Results A total of 13 active ingredients were identified, and 33 targets of CHF were predicted. Network analysis highlighted BSS as the key active ingredient, interacting with 29 targets. GO and KEGG analyses indicated significant involvement of these targets in calcium and apoptosis signaling pathways. Experimental findings demonstrated that BSS enhanced cell viability, reduced intracellular calcium ion concentration, and inhibited caspase 3 activity in Dox-induced H9c2 cells. BSS significantly altered the expression of CHRM1, CASP3, and CASP9 genes ( P < .05), and increased CHRM2 expression. Additionally, BSS significantly increased cTn-I concentration. Notably, suppression of calcium and apoptosis signaling pathways partially mitigated BSS's effects on cell viability and cTn-I concentration. Conclusion Through network pharmacology and experimental verification, establishes BSS as a key active ingredient in the periplocae cortex for CHF treatment. BSS appears to modulate calcium and apoptosis signaling pathways, thereby exerting therapeutic effects in the treatment of CHF.

Highly in vitro anti-cancer activity of melittin-loaded niosomes on non-small cell lung cancer cells

BackgroundDevelopment of promising medicines from natural sources, specially venom, is of highly necessitated to combat against life-threatening cancers. Non-small cell lung cancer (NSCLC) has a significant percentage of mortalities. Melittin, from bee venom, is a potent anticancer peptide but its toxicity has limited its therapeutic applications. Accordingly, this study aims to synthesize niosomes with suitable stability and capacity for carrying melittin as a drug. Additionally, it seeks to evaluate the anti-cancer activity of melittin-loaded niosomes on non-small cell lung cancer. MethodsThe niosome was prepared by thin film hydration method. Cytotoxicity and apoptosis were assessed on A549, Calu-3, and MRC5 cells. Real-time PCR was used to determine expression of apoptotic and pro-apoptotic Bax, Bcl2, and Casp3 genes. Immunocytochemistry (ICC) was also used to confirm expression of the abovementioned genes. Furthermore, wound healing assay was performed to compare inhibition effects of melittin-loaded niosomes with free melittin on migration of cancer cells. ResultsIC50 values of melittin-loaded niosomes for A549, Calu-3, and MRC5 cells were respectively 0.69 μg/mL, 1.02 μg/mL, and 2.56 μg/mL after 72 h. Expression level of Bax and Casp3 increased ‘10 and 8’ and ‘9 and 10.5’ fold in A549 and Calu-3, whereas Bcl2 gene expression decreased 0.19 and 0.18 fold in the mentioned cell lines. The cell migration inhibited by melittin-loaded niosomes. ConclusionsMelittin-loaded niosomes had more anti-cancer effects and less toxicity on normal cells than free melittin. Furthermore, it induced apoptosis and inhibited cancer cells migration. Our results showed that melittin-loaded niosomes may be a drug lead and it has the potential to be future developed for lung cancer treatment.

The mechanism of action and experimental verification of Gan-song Yin on renal clear cell carcinoma based on network pharmacology and bioinformatics

BackgroundGan-song Yin (GSY) is originated from the scripture “Gan-song Pills”, a medical work of the Ningxia ethnic minorities, and its treatment of kidney diseases has good results. Its method of treating Renal clear cell carcinoma (KIRC) is still unknown, nevertheless.MethodsFirstly, utilizing a network pharmacology strategy to screen GSY for active components and targets and looking up KIRC-related targets in GeneCards and GEO databases. Secondly, protein interaction networks were constructed and analyzed for GO and KEGG enrichment. Molecular docking was then performed and clinical and other correlations of the network pharmacology results were analyzed using bioinformatic analysis methods. Finally, we performed in vitro cellular experiments with 786-O cells and ACHN cells to validate the results of network pharmacology and bioinformatic analysis.ResultsWith the help of network pharmacological analysis, six hub targets were eliminated. Bioinformatics study revealed that the hub targets has clinically significant clinical guiding importance. The results showed that GSY inhibited the proliferation of 786-O cells and ACHN cells, induced cell apoptosis, blocked cell cycle, and reduced cell colony formation ability. qRT-PCR results showed that GSY promoted the expression of ALB and CASP3 genes, and inhibited the expression of EGFR, JUN, MYC and VEGFA genes. Western blot results showed that GSY could promote the expression of ALB and CASP3 protein, and inhibit the expression of EGFR, JUN, MYC and VEGFA protein.ConclusionsNetwork pharmacology and bioinformatics analysis showed that GSY could act on multiple targets through a variety of components to achieve the effect of treating KIRC. In this study, we confirmed that GSY inhibits KIRC by regulating the expression of core targets through in vitro cellular experiments, thus providing a reference for subsequent related studies.

Molecular and behavioural responses of the mussel Mytilus edulis exposed to a marine heatwave

Marine heatwaves (MHW) threaten marine organisms and tend to increase in frequency and intensity. We exposed the blue mussel Mytilus edulis to a MHW lasting 23 days, including two 10-d periods of thermal intensity increase of +5 °C (20 °C–25 °C) interspersed by 1 day back to 20 °C, followed by a 4-d recovery period. We investigated behaviour responses of mussels and gene expression changes relative to the circadian rhythm (Per), oxidative stress (SOD), cellular apoptosis (CASP3), energy production (ATPs), and general stress response (hsp70). Results showed that the MHW disturbed the valve activity of mussels. Particularly, mussels increased the number of valve micro-closures, showing a stressful state of organisms. Mussels also decreased Per, CASP3, ATPs, and Hsp70 gene expression. Some behavioural and molecular effects persisted after the MHW, suggesting a limited recovery capacity of individuals. This work highlighted the vulnerability of M. edulis to a realistic MHW.

Cobalt oxide nanoparticles functionalized with glucose and conjugated to Ellagic acid (Co3O4@Glu-Ellagic acid NPs) induce apoptotic genes in HepG2, liver cancer cell line

Surface modification of metal nanoparticles can be a solution to obtain more efficient and biocompatible drugs. In this study, the anticancer mechanism of cobalt oxide nanoparticles (NPs) functionalized with glucose and conjugated with Ellagic acid (Co3O4@Glu-Ellagic acid NPs) in a liver cancer cell line was investigated. Physicochemical characteristics of NPs were investigated by Fourier-transform infrared spectroscopy (FT-IR), Transmission electron microscopy (TEM), (Scanning Electron Microscopy) SEM, X-Ray diffraction analysis (XRD), Energy Dispersive Spectroscopy mapping (EDS-mapping), Dynamic light scattering (DLS), and zeta potential. Cytotoxicity of Co3O4@Glu-Ellagic acid NPs in normal (THLE2) and cancer (HepG2) hepatocyte cell lines was characterized by MTT and flow cytometry assays. Relative expression of the CASP8, CASP9, and p53 genes was assessed by Real-Time PCR. The synthesized nanoparticles were spherical, without considerable agglomeration, and their size was in the range of 20 to 60 nm. Surface charge and DLS size were − 30.1 mV and 280 nm, respectively. Treatment of the studied cells with the nanoparticles displayed their antiproliferative potential; however, liver cancer cells were considerably more sensitive to the nanoparticles than normal hepatocyte cells. The 50 % inhibitory concentration of Co3O4@Glu-Ellagic acid NPs for normal and cancer hepatocyte cells were 201 and 97 μg/mL, respectively. Treating HepG2 cells with Co3O4@Glu-Ellagic acid NPs led to a significant increase in the percentage of apoptotic cells (from 0.66 % to 50.8 %) and expression of the CASP8, CASP9, and p53 genes by 2.88, 2.11, and 2.0 folds that suggests apoptogenic property of the nanoparticles through activation of the intrinsic and extrinsic apoptosis pathways. Measuring Reactive Oxygen Species (ROS) level showed that in treated cancer cells with Co3O4@Glu-Ellagic acid nanoparticles the ROS level increased. Moreover, Hoechst staining indicated the anti-tumor effect of Co3O4@Glu-Ellagic acid NP by appearance of apoptotic bodies in HepG2 cells. This work revealed that Co3O4@Glu-Ellagic acid NPs are potent apoptogenic agent against liver cancer cells.

Silver nanoparticle functionalized by glutamine and conjugated with thiosemicarbazide induces apoptosis in colon cancer cell line

The high mortality rate of colon cancer indicates the insufficient efficacy of current chemotherapy. Thus, the discussion on engineered metal nanoparticles in the treatment of the disease has been considered. In this study, silver nanoparticles were functionalized with glutamine and conjugated with thiosemiccarbazide. Then, anticancer mechanism of Ag@Gln-TSC NPs in a colon cancer cell line (SW480) was investigated. Characterizing Ag@Gln-TSC NPs by FT-IR, XRD, EDS-mapping, DLS, zeta potential, and SEM and TEM microscopy revealed that the Ag@Gln-TSC NPs were correctly synthesized, the particles were spherical, with surface charge of − 27.3 mV, high thermal stability and low agglomeration level. Using MTT assay we found that Ag@Gln-TSC NPs were significantly more toxic for colon cancer cells than normal fibroblast cells with IC50 of 88 and 186 µg/mL, respectively. Flow cytometry analysis showed that treating colon cancer cells with Ag@Gln-TSC NPs leads to a considerable increase in the frequency of apoptotic cells (85.9% of the cells) and increased cell cycle arrest at the S phase. Also, several apoptotic features, including hyperactivity of caspase-3 (5.15 folds), increased expression of CASP8 gene (3.8 folds), and apoptotic nuclear alterations were noticed in the nanoparticle treated cells. Furthermore, treating colon cancer cells with Ag@Gln-TSC NPs caused significant down-regulation of the HULC Lnc-RNA and PPFIA4 oncogene by 0.3 and 0.6 folds, respectively. Overall, this work showed that Ag@Gln-TSC NPs can effectively inhibit colon cancer cells through the activation of apoptotic pathways, a feature that can be considered more in studies in the field of colon cancer treatment.

Study on pyroptosis-related genes Casp8, Gsdmd and Trem2 in mice with cerebral infarction.

Cerebral infarction is the main cause of death in patients with cerebrovascular diseases. Our research aimed to screen and validate pyroptosis-related genes in cerebral infarction for the targeted therapy of cerebral infarction. A total of 1,517 differentially expressed genes (DEGs) were obtained by DESeq2 software analysis. Gene set enrichment analysis results indicated that genes of middle cerebral artery occlusion (MCAO) mice aged 3 months and 18 months were enriched in pyroptosis, respectively. Differentially expressed pyroptosis-related genes (including Aim2, Casp8, Gsdmd, Naip2, Naip5, Naip6 and Trem2) were obtained through intersection of DEGs and genes from pyroptosis Gene Ontology Term (GO:0070269), and they were up-regulated in the brain tissues of MCAO mice in GSE137482. In addition, Casp8, Gsdmd, and Trem2 were verified to be significantly up-regulated in MCAO mice in GSE93376. The evaluation of neurologic function and triphenyltetrazolium chloride staining showed that the MCAO mouse models were successfully constructed. Meanwhile, the expressions of TNF-α, pyroptosis-related proteins, Casp8, Gsdmd and Trem2 in MCAO mice were significantly up-regulated. We selected Trem2 for subsequent functional analysis. OGD treatment of BV2 cell in vitro significantly upregulated the expressions of Trem2. Subsequent downregulation of Trem2 expression in OGD-BV2 cells further increased the level of pyroptosis. Therefore, Trem2 is a protective factor regulating pyroptosis, thus influencing the progression of cerebral infarction. Casp8, Gsdmd and Trem2 can regulate pyroptosis, thus affecting cerebral infarction.

Selenium mitigates methotrexate-induced testicular injury: Insights from male NMRI mice model.

Chemotherapy, particularly with methotrexate (MTX), often elicits testicular toxicity, leading to impaired spermatogenesis and hormone imbalances. This study aimed to investigate the potential protective effects of selenium (Se) against MTX-induced testicular injury. Male mice were divided into control, MTX, Se, and MTX + Se groups. Histopathological examination involved the preparation of testicular tissue sections using the Johnsen's tubular biopsy score (JTBS) for spermatogenesis evaluation. Biochemical tests included the assessment of testosterone, malondialdehyde (MDA), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels. Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to analyze the expression of caspase 3 (casp3), tumor protein 53 (p53), B-cell lymphoma 2 (Bcl2), and Bcl2-associated X protein (Bax) genes. Statistical analysis was performed using ANOVA and Tukey's tests (p < .05). Histopathological analysis revealed significant testicular damage in the MTX group, with decreased spermatogenesis and Leydig cell count, while Se administration mitigated these effects, preserving the structural integrity of the reproductive epithelium. Biochemical analysis demonstrated that MTX led to elevated malondialdehyde (MDA) levels and reduced testosterone, LH, and FSH levels, suggesting oxidative stress and Leydig cell dysfunction. Gene expression analysis indicated that MTX upregulated proapoptotic genes (casp3, p53, and bax) while downregulating the antiapoptotic Bcl2 gene. In contrast, Se treatment reversed these trends, highlighting its potential antiapoptotic properties. Our findings underscore the potential of Se as a therapeutic agent to mitigate the reproductive toxicity associated with MTX-induced testicular injury. Se exerts protective effects by regulating oxidative stress, preserving hormone balance, and modulating apoptotic pathways. These results suggest that Se supplementation could be a promising strategy to alleviate chemotherapy-induced testicular damage and preserve male fertility.

Exploring the apoptotic effects of sericin on HCT116 cells through comprehensive nanostring transcriptomics and proteomics analysis

Sericin, a silk protein from Bombyx mori (silkworms), has many applications, including cosmetics, anti-inflammation, and anti-cancer. Sericin complexes with nanoparticles have shown promise for breast cancer cell lines. Apoptosis, a programmed cell death mechanism, stops cancer cell growth. This study found that Sericin urea extract significantly affected HCT116 cell viability (IC50 = 42.00 ± 0.002 µg/mL) and caused apoptosis in over 80% of treated cells. S-FTIR analysis showed significant changes in Sericin-treated cells' macromolecule composition, particularly in the lipid and nucleic acid areas, indicating major cellular modifications. A transcriptomics study found upregulation of the apoptotic signaling genes FASLG, TNFSF10, CASP3, CASP7, CASP8, and CASP10. Early apoptotic proteins also showed that BAD, AKT, CASP9, p53, and CASP8 were significantly upregulated. A proteomics study illuminated Sericin-treated cells' altered protein patterns. Our results show that Sericin activated the extrinsic apoptosis pathway via the caspase cascade (CASP8/10 and CASP3/7) and the death receptor pathway, involving TNFSF10 or FASLG, in HCT116 cells. Upregulation of p53 increases CASP8, which activates CASP3 and causes HCT116 cell death. This multi-omics study illuminates the molecular mechanisms of Sericin-induced apoptosis, sheds light on its potential cancer treatment applications, and helps us understand the complex relationship between silk-derived proteins and cellular processes.

CRISPR/Cas genome editing revealed non-angiogenic role of VEGFA gene in porcine luteal cells: a preliminary report.

The angiogenic cytokine vascular endothelial growth factor A (VEGFA) also exerts non-angiogenic effects on endocrine functionality of porcine luteal cells critical for progesterone (P4) production. The expression dynamics of VEGFA-FLT/KDR system were investigated using RT-qPCR during luteal stages and VEGFA gene knock out (KO) porcine luteal cells were generated using CRISPR/Cas9 technology. The downstream effects of VEGFA ablation were studied using RT-qPCR, Annexin V, MTT, ELISA for P4 estimation and scratch wound assay. Bioinformatics analysis of RNA-Seq data of porcine mid-luteal stage was conducted for exploring protein-protein interaction network, KEGG pathways, transcription factors and kinase mapping for VEGFA-FLT/KDR interactomes. The VEGFA-FLT/KDR system expressed throughout the luteal stages with highest expression during mid- luteal stage. Cellular morphology, structure and oil-red-o staining for lipid droplets did not differ significantly between VEGFA KO and wild type cells, however, VEGFA KO significantly decreased (p < 0.05) viability and proliferation efficiency of edited cells on subsequent passages. Expression of apoptotic gene, CASP3 and hypoxia related gene, HIF1A were significantly (p < 0.05) upregulated in KO cells. The relative mRNA expression of VEGFA and steroidogenic genes STAR, CYP11A1 and HSD3B1 decreased significantly (p < 0.05) upon KO, which was further validated by the significant (p < 0.05) decrease in P4 output from KO cells. Bioinformatics analysis mapped VEGFA-FLT/KDR system to signalling pathways associated with steroidogenic cell functionality and survival, which complemented the findings of the study. The ablation of VEGFA gene resulted in decreased steroidogenic capability of luteal cells, which suggests that VEGFA exerts additional non-angiogenic regulatory effects in luteal cell functionality.

Synergistic effects of bee venom, hesperidin, and piperine with tamoxifen on apoptotic and angiogenesis biomarker molecules against xerographic MCF-7 injected rats

Breast cancer ranks as the second leading most significant of mortality for women. Studies have demonstrated the potential benefits of natural compounds in cancer treatment and prevention, either in isolation or in conjunction with chemotherapy. In order to improve Tamoxifen's therapeutic efficacy in in-vivo studies, our research sought to determine the effects of hesperidin, piperine, and bee venom as natural compounds, as well as their combination effect with or without Tamoxifen. First, 132 female albino rats were equally divided into six groups and five subgroups, and breast cancer was induced in the selected groups by xenografting of MCF7 cells. Second, the effect of single and best ratio combinations treatment from previous in vitro studies were selected. Next, tumorous mammary glands were collected for apoptotic and antiapoptotic biomarkers and cell cycle analysis. Single or combined natural products with or without Tamoxifen revealed a significant up-regulation in apoptotic genes Bax and Casp3 and a downregulation of antiapoptotic and angiogenesis genes Bcl-2 and VEGF genes. We found that cell cycle arrest in the G0/G1 phase was exclusively caused by Tamoxifen and/ or hesperidin. However, the cell cycle arrest in the G2/M phase is a result of the combination of piperine and bee venom, with or without Tamoxifen by using the flow cytometric technique. Our research concludes that bee venom, hesperidin, and piperine can synergistically enhance to increase Tamoxifen's efficiency in the management of breast cancer.

"Combination treatments of imatinib with astaxanthin and crocin efficiently ameliorate antioxidant status, inflammation and cell death progression in imatinib-resistant chronic myeloid leukemia cells".

Imatinib resistance remains a major obstacle in the treatment of chronic myelogenous leukemia (CML). Crocin (CRC) and astaxanthin (ATX) are phytochemicals with anti-cancer properties. This study aimed to explore the effects of combination treatment of Imatinib with CRC and ATX on Imatinib-resistant K562 (IR-K562) cells. After the establishment of IR-K562 cells, growth inhibitory activity was determined by the MTT assay. To test the regeneration potential, a colony formation assay was performed. Cell cycle analyses were examined by flow cytometry. Cell injury was evaluated by lactate dehydrogenase (LDH) leakage. Real-time PCR was applied to assess the expression of IL6, TNF-α, STAT3, BAD, CASP3, TP53, and Bcl-2 genes. Caspase-3 activity was determined by a colorimetric assay. Antioxidant activity was measured using a diphenylpicrylhydrazyl (DPPH) assay. After 48h of treatment, ATX (IC50 = 30µM) and CRC (IC50 = 190µM) significantly inhibited cell proliferation and colony formation ability, induced G1 cell cycle arrest and cell injury, upregulated the expression of apoptosis-associated genes, and downregulated the expression of anti-apoptotic and inflammatory genes. The combination of IM with ATX and/or CRC synergistically reduced cell viability (combination index [CI] < 1). Our data suggest that IM shows better therapeutic efficacy at lower doses when combined with ATX and/or CRC.

Doxorubicin-sanguinarine nanoparticles: formulation and evaluation of breast cancer cell apoptosis and cell cycle

Background Therapeutic resistance fails cancer treatment. Drug-nanoparticle combinations overcome resistance. Sanguinarine-conjugated nanoparticles may boost sanguinarine’s anticancer effects. Methods Sanguinarine, HPMC-NPs, and doxorubicin were tested on Adriamycin-resistant MCF-7/ADR breast cancer cells, parent-sensitive MCF-7, and MCR-5 normal cells (DX). Results Regular distribution, 156 nm diameter, <1 μm average size, 100% intensity—SN is therapeutic. Furthermore, the obtained NPs showed PDI = 0.145, zeta-potential=-37.6, and EE%=90.5%. DX sensitized MCF-7 cells (IC50 = 1.4 μM) more than MCF-7/ADR cells (IC50 = 27 μM) with RR = 19.3. SA and SN were more toxic to MCF-7/ADR cells (overexpressed with P-gp) than their sensitive parent MCF-7 cells (IC50 = 4 μM, RR = 0.6 and 0.6 μM, RR = 0.7). MCR-5 normal lung cells were more resistant to SA (IC50 = 7.2 μM) and SN (IC50 = 1.6 μM) with a selection index > 2. Synergistic cytotoxic interactions reduced the IC50 from 27 μM to 1.6 (CI = 0.1) and 0.9 (CI = 0.4) after DX and nontoxic dosages (IC20) of SA and SN. DS and SN killed 27.1% and 39.4% more cells than DX (7.7%), SA (4.9%), SN (5.5%), or untreated control (0.3%). DS and DSN lowered CCND1 and survival in MCF-7/ADR cells while raising p21 and Casp3 gene and protein expression. Conclusions Cellular and molecular studies suggested adjuvant chemosensitizers SA and SN to reverse MDR in breast cancer cells.

The Nephroprotective Activity of Boesenbergia Rotunda Rhizome by Reducing Creatinine, Urea Nitrogen, Glutamic Pyruvic Transaminase, and Malondialdehyde Levels in the Blood and Attenuating the Expression of Havcr1 (KIM-1), Lcn2 (NGAL), Casp3, and Casp7 Genes in the Kidney Cortex of Cisplatin-Induced Sprague-Dawley Rats.

Cisplatin chemotherapy induces nephrotoxicity by producing reactive oxygen species, hence, discovering add-on nephroprotective drugs for patients with cancer is challenging. Boesenbergia rotunda has been reported for its antioxidant properties. This study aims to explore the nephroprotective mechanism of the ethanol extract of Boesenbergia rotunda rhizome (EEBR) in cisplatin-induced rats. The rats were randomly assigned into 6 groups: the normal control (treated with saline); the negative control (cisplatin-induced without any treatment); the positive control (treated with quercetin 50 mg/kg BW); and 3 treatment EEBR (125 mg/kg BW; 250 mg/kg BW; 500 mg/kg BW) groups for 10 days. The % relative organ weight, kidney histopathology, and nephrotoxicity biomarkers expression were evaluated. EEBR decreased creatinine, urea nitrogen, glutamic pyruvate transaminase, and malondialdehyde levels in the blood of cisplatin-induced rats. An insignificant increase in GOT was observed in rats treated with the highest dose of EEBR. EEBR did not significantly alter the BW and the % kidney relative weight. An abnormal shape of the Bowman capsule is observed in the negative control group. EEBR reduced the expression of Havcr1 (KIM-1), Lcn2 (NGAL), Casp3, and Casp7 genes in rats' kidneys. Boesenbergia rotunda could be considered a potential candidate for add-on therapy in cisplatin-treated patients, but further studies are needed to verify its efficacy and safety.

Evaluation of the Cytotoxicity of Secondary Bioactive Compounds Produced by Streptomyces in Soil against a Colon Cancer Cell Line.

Colorectal cancer is one of the most serious malignancies affecting humans. In this study, Streptomyces bioactivechemicals extracted from soil were analyzed for their anti-colorectal-cancer and antibacterial properties. A total of 100 soil samples were collected from Kerman-Iran, incubated in SCA media and the antimicrobial properties were tested using the cross-streak method. Three strains were cultured in ISP4 medium to obtain secondary bioactive compounds. After studying the effects of the bioactive compounds on the HT29 and human foreskin fibroblast (HFF) cell lines, the expression of the p53, p21, BAX, BCL2, Casp3 and Casp8 genes was analyzed by real-time PCR and flow cytometry to detect the presence of apoptosis.The isolates show high degree of identification with Streptomyces rochei, Streptomyces fungicidicus and Streptomyces maritimus due to 16SrDNA sequence homology. Compared to HT-29 cells, Streptomyces extracts had lower cytotoxicity against normal cells (SI=5.88), followed by HFF (SI=4.14). The cell lines demonstrated a dose-dependent significant increase in DNA fragmentation, an increase in the proportion of cells in sub-G1 phase and caused G2/M cell cycle arrest in HT-29 and HFF cells.The bacterial extracts obtained displayed strong antibacterial properties and inhibited the proliferation of HT-29 and HFF cell lines. The treated cells exhibited morphological changes caused by the activation of caspase and p53/p21 proteins. This confirms that Streptomyces-induced apoptosis is mediated by the activation of p21/p53. Anti-apoptotic Bcl-2 gene expression was downregulated by treatment with the extracts. Further studies are needed to understand the antimicrobial properties of Streptomyces.

The key role of vitamin C in the treatment of pulmonary hypertension of meat-type chickens: role of caspase-3

Ascites is a prominent example of the pathophysiological interaction between the heart and lungs in broilers. Previous experiments have shown that the amount of apoptosis increases in heart failure and pulmonary hypertension. In the current study, the effect of vitamin C on apoptosis was investigated by measuring the expression of the CASP3 gene in the heart and lungs of chickens with ascites. For this purpose, 90 one-day-old meat-type chickens were divided into three groups (sham (basal diet), control (basal diet +1.5 mg/kg of triiodothyronine (T3)), and treatment group (basal diet + 1.5 mg/kg of T3 + 1200 ppm of vitamin C)) and bred for 49 days. On the 21st and 49th days after rearing, 15 chickens from each group were selected randomly, and the right ventricle/ total ventricle weight ratio (RV/TV), as well as the expression level of CASP3 genes in the lung and right ventricle of all groups were measured and compared. The amount of mRNA related to CASP3 gene at the age of 21 and 49 days demonstrated a meaningful decrease in the treatment group compared to the control group (P&lt;0.05). This significant difference indicates the reduction of apoptosis in the group treated with vitamin C. Also, RV/TV as an index of the induction of this syndrome improved in the treatment group at the age of 21 and 49 days (P&lt;0.05). Finally, according to the current study's findings, vitamin C has ameliorating effects in treating ascites in meat-type chickens.

Biological activities of Liquidambar orientalis: Antibiofilm, cytotoxicity, apoptosis, and miRNA expressions

Due to its strong biological, pharmacological, and medical activities and rich chemical content, Liquidambar orientalis, known for its resinous exudate storax, has a widespread and well-established ethnopharmacological use. Although it is known that storax has anticancer, antimicrobial, antioxidant, wound-healing and other ethnomedicinal properties, the number of existing scientific studies is very limited. In this context, the aims of this study were to determine the antibiofilm activity of storax and its cytotoxic and apoptotic effects in A549 lung cancer cells. In addition, with this study, it is also possible to make a very comprehensive biological evaluation by determining the effect of storax on certain microRNA expressions. According to our results, L. orientalis storax decreases cell proliferation in A549 lung cancer cells and the IC50 value was determined at 31.5 ?g/mL at 24h. Storax also induces apoptosis via upregulating CASP3, 8, 9, and Bax gene expression and downregulating Bcl-2 expressions in A549 cells. Furthermore, storax decreases the expression of miR-146a, miR-21, and miR-223, while increasing the expression of miR-155. Storax inhibits biofilm formation and reduces the preformed biofilm of microbial strains including Staphylococcus aureus (ATCC 33862), Pseudomonas aeruginosa (ATCC 27853) and Candida albicans (ATCC 64548). The results suggest that storax has strong cytotoxic, apoptotic and antibiofilm properties and thus promising potential in medicine.

Apoptotic effect of thymoquinone on OVCAR3 cells via the P53 and CASP3 activation.

The limitations in cancer treatment and the inadequacy of classical methods have made it necessary to discover therapeutics in cancer treatment. The cytotoxicity of thymoquinone, which has quite different properties in terms of biological activities, in ovarian cancer cells, and the changes in the expression levels of apoptotic genes (p53/caspase-3 (casp-3)) were investigated. In the study, thymoquinone (5, 50, 100, 250 and 500 µM and 24, 48, 72 hours) were applied to ovarian adenocarcinoma cancer cell line (OVCAR3), at different concentrations. Cytotoxic effect of thymoquinone on OVCAR-3 cells were analyzed by MTT method, and apoptotic and pro-apoptotic gene expression levels (p53, Casp-3) of thymoquinone in cancer cells were analyzed by quantitative real-time polymerase chain reaction. Thymoquinone, whose effect has been revealed in many types of cancer, was shown to significantly reduce the viability of OVCAR3 cancer cells depending on the dose and time (p < 0.05). It was also determined that Casp-3 and p53 gene expressions increased in OVCAR3 cells. Considering the in-vitro cytotoxic activity and apoptotic gene expressions of thymoquinone, an important treatment agent, since it is a promising agent for the future of cancer treatment, more comprehensive studies may pave the way for its clinical use.