Caspase-3 Gene Research Articles

Cytotoxic activity of silver nanoparticles prepared by eco-friendly synthesis using Lythrum salicaria extract on breast cancer cells.

Metal nanoparticles (NPs) have widely been investigated due to their several applications in therapeutic activities. The current investigation highlights the cytotoxic effects of the eco-friendly phytosynthesis route for silver nanoparticles using Lythrum salicaria (L. salicaria) extract (AgNPs-LS). The change in color from colorless to brown confirmed the reduction of silver ions to AgNPs. x-ray diffraction (XRD) analysis demonstrated high crystallinity. The surface morphology of AgNPs-LS was spherical, and their average sizes were 50nm. energy-dispersive x-ray analysis (EDAX) confirmed that silver was the predominant component, indicating the involvement of L. salicaria plant extract in the green synthesis process. In vitro dimethyl thiazolyl tetrazolium bromide (MTT) assay showed significant cytotoxicity of AgNPs-LS against MCF7 cells, with an IC50 of 113µg mL- 1. In contrast, AgNPs-LS showed minimal cytotoxicity to HEK293 cells (IC50: 254µg mL- 1), demonstrating a higher sensitivity of cancer cells to AgNPs-LS. Moreover, AgNPs-LS resulted in MCF7 cells producing reactive oxygen species (ROS) and undergoing cell cycle arrest at the G2/M phase, serving as barriers to the proliferation of cancer cells. Annexin V fluorescein isothiocyanate (FITC) assays and fluorescence microscopy confirmed the induction of apoptosis in MCF7 cells by AgNPs-LS. Gene expression analysis revealed upregulated pro-apoptotic genes (Bax, p53, caspase-3, and caspase-9) and downregulated an anti-apoptotic gene (Bcl2) in michigan cancer foundation7 (MCF7) cells treated with AgNPs-LS. These results indicate that AgNPs-LS induced apoptosis via the intrinsic pathway (mitochondrial-mediated mechanism) and involved p53-dependent regulation. The current study results implied that AgNPs-LS fabricated by a bio-green approach could be helpful to the future of nanomedicine.

Clemastine mitigates sepsis-induced acute kidney injury in rats; the role of α-Klotho/TLR-4/MYD-88/NF-κB/ Caspase-3/ p-P38 MAPK signaling pathways

Sepsis is a fatal condition, with an annual incidence of more than 48 million cases as well as 11 million deaths resulting from it. Moreover, sepsis continues to rank as the fifth most prevalent cause of mortality globally. The objective of this study is to investigate if Clemastine (CLM) pretreatment protects against acute kidney injury (AKI) caused by cecal ligation and puncture ( CLP) via modulating Toll-like receptor-4 (TLR-4), Myeloid differentiation primary response 88 (MYD-88), nuclear factor kappa B (NF-κB), Bcl-2-associated X (Bax), B-cell lymphoma-2 (Bcl-2), and caspase-3 signaling pathways. CLM markedly attenuated sepsis-caused molecular, biochemical, and histopathological alterations. CLM downregulated the levels of the proinflammatory markers, suppressed the expression of cleaved caspase-3, TLR-4 and MYD-88 as well as inactivating NF-κB p-P65 and p-P38 proteins, inhibited Bax, NF-κB, and caspase-3 genes expression, and augmented α-Klotho protein expression as well as Bcl-2 gene expression. Finally, CLM pretreatment protected against acute kidney injury by preventing TLR-4/ p-P38 pathway-mediated apoptotic cell death in rats.

Exploring acenocoumarol and silodosin as allosteric EGFR inhibitors for the treatment of non-small cell lung cancer

Background Non-small-cell lung cancer (NSCLC) is a highly morbid disease. Chemotherapy for NSCLC lacks specificity and efficacy mainly because of drug resistance. The current study aimed to explore computational tools to target allosteric epidermal growth factor receptor (EGFR) sites and screen for the top molecules in vitro and in vivo xenograft models. Methods Molecular docking, virtual screening, and molecular dynamic studies revealed that acenocoumarol and silodosin are the top two allosteric EGFR inhibitors. They were further tested for cytotoxicity, apoptosis, cell cycle, and gene expression by qPCR, western blotting, A549 cell xenograft anti-proliferative activity, and tumor regression efficacy analysis. Results Acenocoumarol and silodosin exhibited cytotoxicity in A549 and IMR-90 cells at concentrations below 50 and 80 μM, respectively. Acenocoumarol and silodosin induced S-phase and G2/M-phase arrest in A549 cells in the cell cycle analysis. Both drugs showed early apoptosis at their IC50 doses (acenocoumarol 50 μM and silodosin 25 μM). KRAS (Kirsten rat sarcoma viral oncogene homolog) and ERK2 (extracellular signal-regulated kinase 2) gene regulation in A549 cells was confirmed using qPCR. KRAS and ERK2 activities were quantified by western blot analysis. In the xenograft study, tumor size, body weight, and organ weight were significantly attenuated by the test drugs compared with the standard cisplatin. Immunoblotting and western blot results of the A549-xenograft tissue indicated downregulation of KRAS and ERK2. Furthermore, the test drugs have upregulated caspase-3 gene expression. Conclusion The drugs acenocoumarol and silodosin downregulate KRAS and ERK2 both in cell line and in Xenograft model. KRAS and ERK2 are associated with EGFR inhibition. Hence, acenocoumarol and silodosin can be further explored for repurposing studies in human trials.

The ability of the Lab4 probiotic consortium to impact upon the functionality of serum deprived human keratinocytes in vitro

IntroductionDysfunction of keratinocytes contributes to a weakened skin barrier and impaired wound healing capability. Evidence suggests that probiotic supplementation can lead to improved skin function in vitro and in vivo. The Lab4 probiotic consortium comprises of two strains of Lactobacillus species and two strains of Bifidobacterium species.MethodsUsing serum deprived conditions to impair the functionality of immortalized human HaCaT keratinocytes, this study aimed to assess the impact of metabolites derived from the Lab4 probiotic consortium on keratinocyte function.ResultsA significant improvement in HaCaT metabolic activity and lower apoptotic activity was observed in tandem with a reduction in Caspase-3 gene expression and a lower Bax/Bcl2 ratio following the addition of Lab4. The probiotic also supported barrier integrity which was better maintained with a significant increase in Filaggrin gene expression. In damaged keratinocytes, Lab4 enhanced rates of re-epithelialization, which were associated with significantly increased gene expression of MMP-1 and enhanced secretion of IL-6 and IL-8.DiscussionThese results suggest that the Lab4 probiotic consortium may have the ability to benefit the functionality of skin.

Effects of Density Stress During Transportation on the Antioxidant Activity and Immuno-Related Gene Expression in Yellowfin Seabream (Acanthopagrus latus Houttuyn, 1782).

Background/Objectives: Maintaining an optimum transport density is essential for protecting water quality, lowering stress levels, and increasing fish survival rates. Transporting marine fish fry involves major dangers. The purpose of this study was to evaluate the impact of transport stress at varying densities on the immune-related gene expression, antioxidant capacity, and survival rate of yellowfin seabream (Acanthopagrus latus) fry. Methods: A 12 h simulated transport experiment was conducted with A. latus fry divided into six density groups. For 1-2 cm fry, densities of 900, 1200, and 1500 fry per pouch were used to assess antioxidant enzyme activity; and for 4-5 cm fry, densities of 100, 125, and 150 fry per pouch were used for gene expression analysis. The key parameters measured included survival rates, antioxidant enzyme activities in liver and intestinal tissues, and expression levels of HSP90α and caspase-3 genes. Results: The findings showed that recovery time and density both affected the observed responses and that transport density had a substantial effect on antioxidant enzyme activity in all tissues. The intestinal and liver tissues showed a considerable decrease in antioxidant enzyme activity, suggesting that these tissues may be able to respond to oxidative stress. Moreover, under high-density transport conditions, there were notable increases in the expression of caspase-3 and HSP90α, suggesting the activation of immune response systems. This research offers valuable new understandings into the relationship between transport density and immunological and antioxidant modulation in A. latus fry. Conclusions: The results provide a scientific foundation for enhancing aquaculture transport conditions, which will ultimately lead to decreased fish mortality and improved general health during transit, resulting in more sustainable and effective aquaculture methods.

Unveiling the Anticancer Potential of a New Ciprofloxacin-Chalcone Hybrid as an Inhibitor of Topoisomerases I & II and Apoptotic Inducer.

The current study has yielded promising results in the evaluation of a new ciprofloxacin-chalcone hybrid (CP derivative) for its anticancer activity as potential Topoisomerases (Topo) I and II inhibitors. The in vitro results showed that the CP derivative significantly suppressed the growth of HCT-116 and LOX IMVI cells, with IC50 values of 5.0 μM and 1.3 μM, respectively, outperforming Staurosporine, which had IC50 values of 8.4 μM and 1.6 μM, respectively. Flow cytometry analysis revealed that the new CP derivative triggered apoptosis and cell cycle arrest at the G2/M phase, associated with the up-regulation of pro-apoptotic genes (Bax and Caspase 9) and downregulation of the anti-apoptotic gene (Bcl-2). Further investigations showed that the CP derivative inhibited Topo I and II enzymes, as expected molecular targets; docking studies further supported its dual inhibitory action on Topo I and II. These findings suggest that the ciprofloxacin-chalcone hybrid could be a promising lead compound for developing new anticancer therapy.

In vitro anti-prostate cancer efficacy and phytochemical composition of the dichloromethane and ethyl acetate leaf extracts of Vitex doniana (sweet).

Prostate cancer is a significant global health concern, particularly among ageing male populations, with a disproportionately higher burden in sub-Saharan Africa. Conventional treatments, though effective, are costly and cause devastating side effects which limit their clinical benefits. Hence, this study evaluated the in vitro antiprostate cancer properties and secondary metabolites of dichloromethane and ethyl acetate lead extracts of Vitex doniana to explore safer and efficacious natural alternatives based on ethnomedicinal claims. Phytochemical profiling was conducted using gas chromatography-mass spectrometry (GC-MS) analysis to identify secondary metabolites in the extracts. The cytotoxic effects of the extracts were determined through the MTT assay using Vero CCL-81 cells and DU-145 cells. The expression profile of the selected genes (ar, bcl2, caspase-3, cdk1, and p53) in DU-145 cells treated with the study extracts was investigated using RT-qPCR. GC-MS analysis revealed 10 secondary metabolites in the dichloromethane extract and 27 secondary metabolites in the ethyl acetate extract of V. doniana leaves, with the majority being sesquiterpenes, diterpenoids, and phytosterols. The dichloromethane and ethyl acetate leaf extracts of V. doniana exhibited low cytotoxicity against normal mammalian epithelial cells (Vero CCL-81), with CC50 values of 1,238.85μg/mL and 964.81μg/mL, respectively. Besides, the ethyl acetate leaf extract of the studied plant demonstrated potent anti-prostate cancer activity against DU-145 cells, with an IC50 of 35.68μg/mL and a high selectivity index (SI) of 27.04. Likewise, the dichloromethane leaf extract of this plant displayed cytotoxic effects (IC50: 287.01μg/mL) and a selectivity index of 4.32. The reference drug (Doxorubicin) showed a higher toxicity against Vero CCL-81(IC50: 0.41μg/mL) and DU-145 (IC50: 0.28μg/mL) cells and a lower selectivity index of 1.46. The DU-145 cells treated with the studied plant extracts exhibited notable upregulation of ar and bcl2, and normalization of caspase 3, cdk1 and p53 expression. The studied plant extracts possess in vitro anti-prostate cancer properties and could be promising candidates for further preclinical studies aimed at developing novel botanical-based therapies for the management of prostate cancer.

P53 and the E3 Ubiquitin Ligase MDM2 in Glaucomatous Lamina Cribrosa Cells.

Lamina cribrosa (LC) cells play an integral role in extracellular matrix remodeling and fibrosis in human glaucoma. LC cells bear similarities to myofibroblasts that adopt an apoptotic-resistant, proliferative phenotype, a process linked to dysregulation of tumor suppressor-gene p53 pathways, including ubiquitin-proteasomal degradation via murine-double-minute-2 (MDM2). Here, we investigate p53 and MDM2 in glaucomatous LC cells. Primary human LC cells were isolated from glaucomatous donor eyes (GLC) and age-matched normal controls (NLC) (n = 3 donors/group). LC cells were cultured under standard conditions ± 48-h treatment with p53-MDM2-interaction inhibitor RG-7112. Markers of p53-MDM2, fibrosis, and apoptosis were analyzed by real-time polymerase chain reaction (qRT-PCR), western blotting, and immunofluorescence. Cellular proliferation and viability were assessed using colorimetric methyl-thiazolyl-tetrazolium salt assays (MTS/MTT). In GLC versus NLC cells, protein expression of p53 was significantly decreased (p < 0.05), MDM2 was significantly increased, and immunofluorescence showed reduced p53 and increased MDM2 expression in GLC nuclei. RG-7112 treatment significantly increased p53 and significantly decreased MDM2 gene and protein expression. GLC cells had significantly increased protein expression of αSMA, significantly decreased caspase-3 protein expression, and significantly increased proliferation after 96 h. RG-7112 treatment significantly decreased COL1A1 and αSMA, significantly increased BAX and caspase-3 gene expression, and significantly decreased proliferation in GLC cells. MTT-assay showed equivocal cellular viability in NLC/GLC cells with/without RG-7112 treatment. Our data suggests that proliferation and the ubiquitin-proteasomal pathway are dysregulated in GLC cells, with MDM2-led p53 protein degradation negatively impacting its protective role.

Chitosan-encapsulated selenium nanoparticles alleviate CCl4 induced hepatotoxicity through synergistically modulating NF-κB and Nrf2 signaling pathways and regulating Bcl-2 and Caspase-3 expression: A comprehensive study with multiple regression analysis

BackgroundThe delivery of selenium in a nano-form (Se-NPs) is a promising modality of treatment for various oxidative stress-induced diseases. ObjectiveThis study aims to investigate the conceivable effects of selenium nanoparticles either alone (Se-NPs) or encapsulated with chitosan (Se-CS-NPs) on toxicity induced by CCl4 in rats. MethodsEighty albino rats were divided equally into eight groups. The first group was the placebo. The second group was a positive control, while the third and the fourth groups got orally (Se-NPs 5 mg/Kg) and (Se-CS-NPs 225 mg/Kg) respectively. The fifth and sixth groups were protective groups in which Se-NPs or Se-CS-NPs were given simultaneously. The seventh and eighth groups were therapeutic as they received either Se-NPs or Se-CS-NPs after stopping the CCl4 injection for 4 weeks more. ResultsOur results showed that the protective and therapeutic groups showed an increase in caspase-3 gene expression with a decline in the expression of Bcl-2, Nrf2, and AFP genes. Histopathological and immunohistochemical investigations showed the role of selenium nanoparticles either alone or coated with chitosan in decreasing fibrotic marker collagen I positive reaction ConclusionSelenium nanoparticles showed an excellent effect in counteracting the toxic effect of carbon tetrachloride on liver functions, inflammation reactions, and apoptosis process. Moreover, using selenium nanoparticles has a strong role in preserving the liver architecture with its normal constituents. No additional benefit was observed when the selenium nanoparticles were encapsulated with chitosan.

Folic Acid Attenuates N-Methyl-N'-Nitro-N-NitrosoguanidineInduced Gastric Mucosal Injury in Rats.

N-Methyl-N'-nitroso-N-nitrosoguanidine (MNNG) is suspected to increase the risk of developing stomach cancer. Folic acid (FA) is familiar with decreasing inflammation. We expected that FA would protect against MNNG-induced gastric mucosal injury. Thirty 12-week-old SPF-grade female Sprague-Dawley (SD) rats were treated with MNNG and given different dosages of FA as an intervention measure. Quantitative polymerase chain reaction (qPCR) was used to analyze the expression of IL-1, IL-6, IL-8, IL-18, TNF-α, NLRP3, ASC, and caspase-1 genes. The enzyme-linked immunosorbent assay (ELISA) was utilized for the identification of inflammatory cytokines. Western blot was accustomed to detecting IL-1β, IL-18, and NLRP3 inflammatory vesicles in gastric tissue. Furthermore, the gastric mucosal tissues underwent histological examination. Our investigation demonstrated that FA reduced MNNG-induced inflammatory factor increase by decreasing NF-κB signaling (P < .05). Furthermore, FA prevented the MNNG-induced upregulation of NLRP3 inflammasome-related genes and proteins (all P < .01). Our data imply that MNNG exposure stimulates the NF-κB/NLRP3 pathway, while FA suppresses it, limiting stomach mucosal inflammation.

Tanshinone II A Facilitates Chemosensitivity of Osteosarcoma Cells to Cisplatin via Activation of p38 MAPK Pathway.

To examine the mechanism of action of tanshinone II A (Tan II A) in promoting chemosensitization of osteosarcoma cells to cisplatin (DDP). The effects of different concentrations of Tan II A (0-80 µ mol/L) and DDP (0-2 µ mol/L) on the proliferation of osteosarcoma cell lines (U2R, U2OS, 143B, and HOS) at different times were examined using the cell counting kit-8 and colony formation assays. Migration and invasion of U2R and U2OS cells were detected after 24 h treatment with 30 µ mol/L Tan II A, 0.5 µ mol/L DDP alone, and a combination of 10 µ mol/L Tan II A and 0.25 µ mol/L DDP using the transwell assay. After 48 h of treatment of U2R and U2OS cells with predetermined concentrations of each group of drugs, the cell cycle was analyzed using a cell cycle detection kit and flow cytometry. After 48 h treatment, apoptosis of U2R and U2OS cells was detected using annexin V-FITC apoptosis detection kit and flow cytometry. U2R cells were inoculated into the unilateral axilla of nude mice and then the mice were randomly divided into 4 groups of 6 nude mice each. The 4 groups were treated with equal volume of Tan II A (15 mg/kg), DDP (3 mg/kg), Tan II A (7.5 mg/kg) + DDP (1.5 mg/kg), and normal saline, respectively. The body weight of the nude mice was weighed, and the tumor volume and weight were measured. Cell-related gene and signaling pathway expression were detected by RNA sequencing and Kyoto Encyclopedia of Genes and Genomes pathway analysis. p38 MAPK signaling pathway proteins and apoptotic protein expressions were detected by Western blot. In vitro studies have shown that Tan II A, DDP and the combination of Tan II A and DDP inhibit the proliferation, migration and invasion of osteosarcoma cells. The inhibitory effect was more pronounced in the Tan II A and DDP combined treatment group (P<0.05 or P<0.01). Osteosarcoma cells underwent significantly cell-cycle arrest and cell apoptosis by Tan II A-DDP combination treatment (P<0.05 or P<0.01). In vivo studies demonstrated that the Tan II A-DD combination treatment group significantly inhibited tumor growth compared to the Tan II A and DDP single drug group (P<0.01). Additionally, we found that the combination of Tan II A and DDP treatment enhanced the p38 MAPK signaling pathway. Western blot assays showed higher p-p38, cleaved caspase-3, and Bax and lower caspase-3, and Bcl-2 expressions with the combination of Tan II A and DDP treatment compared to the single drug treatment (P<0.01). Tan II A synergizes with DDP by activating the p38/MAPK pathway to upregulate cleaved caspase-3 and Bax pro-apoptotic gene expressions, and downregulate caspase-3 and Bcl-2 inhibitory apoptotic gene expressions, thereby enhancing the chemosensitivity of osteosarcoma cells to DDP.

Liposome encapsulating pine bark extract in Nile tilapia: Targeting interrelated immune and antioxidant defense to combat coinfection with Aeromonas hydrophila and Enterococcus faecalis

Application of smart delivery systems for encapsulation of natural ingredients provides novel avenues and is being frequently developed. Thus, we aimed to highlight the effects of cyclosome liposomal pine bark extract (CL-PBE) on Nile tilapia growth, immunomodulation, antioxidant capacity and resistance against coinfection with Aeromonas hydrophila and Enterococcus faecalis and their associated virulence genes. The experiment was conducted on four fish groups receiving a control diet (control) along with three baseline meals supplemented with 200, 400 and 600 mg/kg diet of CL-PBE (CL-PBE 200, 400 and 600, respectively). At the end of the 12-weeks feeding trial, the tilapias were intraperitoneally challenged with virulent A. hydrophila strain and five days later, E. faecalis challenge was carried out. The results revealed that tilapias fed diets fortified with CL-PBE displayed significantly enhanced growth rate and feed conversion ratio in a dose-dependent manner. Moreover, we demonstrated that CL-PBE had potent antioxidant property presented by modulation of several markers of oxidative stress; substantial reductions in reactive oxygen species, hydrogen peroxide and malondialdehyde levels, an elevation in total antioxidant capacity and boosting glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD) activities in fish serum and muscle tissues. This was also correlated with augmenting the expression of CAT, SOD, GSH-Px, Nrf2 and caspase-1 genes alongside reducing those of COX-2, HSP70 and iNOS genes in response to CL-PBE. Our data demonstrated that CL-PBE fortification counteracted the overly pronounced inflammatory response-mediated induction of IL-1β, TNF-α, MHCII and TLR2 genes at the transcriptional levels post coinfection together with promotion in MUC2 and IL-10 genes expression. Notably, our findings displayed optimal well-functioning fish immune system post dietary supplementation of CL-PBE for the protection against coinfection with A. hydrophila and E. faecalis. This was evident from the decline of their counts and hence encompassing the capacity to reduce cumulative mortality percentage in conjunction with interference with their virulence via the significant downregulatory effects of CL-PBE on E. faecalis esp and gelE and A. hydrophila act and fla virulence genes. Taken together, our study strongly suggested dietary inclusion of CL-PBE for Nile tilapias with superior growth performance and significant economic benefits coupled with potent stimulatory effects on antioxidant capacity and immune response expediting our detailed understanding of how coinfection with A. hydrophila and E. faecalis was controlled.

Genome-wide identification, evolution, diversity and expression of Caspase gene family in Haliotis discus hannai

Genome-wide identification, evolution, diversity and expression of Caspase gene family in Haliotis discus hannai

Novel Applicator Utilizing HIFES and Enhanced Synchronized Radiofrequency+ for Subcutaneous Fat Reduction: Porcine Model Study.

Submental fullness has been associated with being perceived as unattractive. Technology combining radiofrequency and muscle stimulation offers submental contouring through fat reduction, muscle stimulation, and skin tightening. This study aims to demonstrate the effectiveness and safety of fat reduction aspect with a novel submentum applicator delivering HIFES and synchronized radiofrequency+ (RF+) energies. Six white pigs (sus scrofa domesticus, n = 6, 60-80 kg) were recruited for this study, five in the active group (n = 5) received four treatments on the abdominal area, one sow served as a control (n = 1). Ultrasound, histological, and RT-qPCR methods were used as evaluation methods. Fat thickness decreased at 1 month by -17.35% and at 2 month by 31.40%. Proapoptotic caspase-9 gene expression increased (at 1 h, 6 h, 24 h to +43.45%, +21.22%, -8.36%), as well as caspase-3 (+15.28%, +21.77%, -6.71%), while bcl2l1 activity decreased (-11.46% at 1 h, -17.02% at 6 h, -3.9% at 24 h). While the AI in the control animal had minimal change (at 1 h -0.08%, at 6 h -0.09%, and at 24 h -0.025%), the active group's AI increased from the baseline of 9.14 to 44.85 at 1 h (+391%), peaked at 6 h to 53.50 (+485%), and at 24 h to 38.17 (+318%). The study results indicate the efficacy and safety of subcutaneous fat reduction following the novel technology combining HIFES and RF+ energies, designed to target small localized areas.

Molecular Docking, Bioinformatic Analysis, and Experimental Verification for the Effect of Naringin on ADHD: Possible Inhibition of GSK-3β and HSP90.

Background/Objectives: One of the most abundant and growing neurodevelopmental disorders in recent decades is attention deficit hyperactivity disorder (ADHD). Many trials have been performed on using drugs for the improvement of ADHD signs. This study aimed to detect the possible interaction of naringin with Wnt/β-catenin signaling and its putative anti-inflammatory and protective effects in the mouse ADHD model based on bioinformatic, behavioral, and molecular investigations. Furthermore, molecular docking was applied to investigate possible interactions with the GSK-3β and HSP90 proteins. Methods: Male Swiss albino mice were divided into four groups, a normal control group, monosodium glutamate (SGL) control, SGL + naringin 50 mg/kg, and SGL + naringin 100 mg/kg. The psychomotor activity of the mice was assessed using the self-grooming test, rope crawling test, and attentional set-shifting task (ASST). In addition, biochemical analyses were performed using brain samples. Results: The results of the SGL group showed prolonged grooming time (2.47-folds), a lower percentage of mice with successful crawling on the rope (only 16.6%), and a higher number of trials for compound discrimination testing in the ASST (12.83 ± 2.04 trials versus 5.5 ± 1.88 trials in the normal group). Treatment with naringin (50 or 100 mg per kg) produced significant shortening in the grooming time (31% and 27% reductions), as well as a higher percentage of mice succeeding in crawling with the rope (50% and 83%, respectively). Moreover, the ELISA assays indicated decreased dopamine levels (0.36-fold) and increased TNF-α (2.85-fold) in the SGL control group compared to the normal mice, but an improvement in dopamine level was observed in the naringin (50 or 100 mg per kg)-treated groups (1.58-fold and 1.97-fold). Similarly, the PCR test showed significant declines in the expression of the Wnt (0.36), and β-catenin (0.33) genes, but increased caspase-3 (3.54-fold) and BAX (5.36-fold) genes in the SGL group; all these parameters were improved in the naringin 50 or 100 mg/kg groups. Furthermore, molecular docking indicated possible inhibition for HSP90 and GSK-3β. Conclusions: Overall, we can conclude that naringin is a promising agent for alleviating ADHD symptoms, and further investigations are required to elucidate its mechanism of action.

Vitamin E improves oxidative stress, apoptosis, and steroidogenesis impairment in glyphosate-induced mice

Background Glyphosate (Gly) is a nonselective pesticide with high potential to toxic effects on the reproductive system. Recent studies suggest that Vitamin E can indeed have a positive impact on the reproductive system, while Gly, a nonselective pesticide, has been linked to significant risks of toxicity on reproductive health. It’s crucial to be mindful of the potential impacts of such substances on the reproductive system. Methods Seventy female mice were categorized into seven groups.: (1) control, (2) olive oil (as Vit E solvent), (3) Vit E, (4) L-Gly, (5) H-Gly, (6) L-Gly + Vit E, and (7) H-Gly + Vit E. Various factors related to oxidative stress, antioxidant activity, steroid hormones, and mRNA expression levels of genes involved in apoptosis and steroidogenesis were assessed. Results After treatment with both doses of Gly, the malondialdehyde level significantly increased in comparison to the control group. Conversely, the activity of catalase and the levels of glutathione, estrogen, and progesterone decreased. Treatment of mice with both doses of Gly resulted in increased mRNA levels of Bax, caspase-3, and caspase-9 genes, as well as a decreased mRNA level of the Bcl-2 gene and factors involved in steroidogenesis (StAR and 3-β-HSD) comparison to the control group. Conclusion These results offer that vitamin E could help improve some of the adverse effects of Gly in the ovaries of female mice.

Arginine alleviates LPS-induced leukocytes inflammation and apoptosis via adjusted NODs signaling

Arginine plays a key role in regulating the immune function of fish. To evaluate the effect of arginine on the immune response of largemouth bass (Micropterus salmoides), the effects of arginine on cell viability, NADPH oxidase activity, respiratory burst activity, and NO production of leukocytes were analyzed both in vitro and in vivo. In this study, we found that arginine could promote the respiratory burst activity of leucocytes both in vivo and in vitro. By incubating leukocytes with the combination of LPS and arginine, we found that arginine supplementation inhibited the expression of inflammatory genes (tumor necrosis factor-alpha, tnfα; interleukin(il) 8 and il10) and apoptotic genes (caspase 3, caspase 8, and caspase 9) induced by LPS, as well as promoted the arginine metabolism. Arginine supplementation significantly induced (cd4-like) cd4 gene expression after LPS challenge. Further studies showed that LPS could significantly increase nucleotide-binding oligomerization domain containing 1 (nod1) gene expression, but decreased the nod2 gene. The arginine supplementation increased nuclear factor kappa-B (NF-κB) protein level. In conclusion, arginine can alleviate LPS-induced inflammatory response and apoptosis as well as induce cd4 gene expression against LPS challenge via adjusting the expression of NODs signaling.

Study on the role of RPL23 gene in active immunity of termite Reticulitermes chinensis against Metarhizium anisopliae

Ribosomal proteins are considered to be involved in the immunity of different animals against pathogens. The protein level of RPL23 increased after fungal infection in termites, but how it influence active immunity in termites is unknown. The role of RPL23 gene was studied to evaluate its impact on active immunity of termite Reticulitermes chinensis against entomopathogenic fungus (EPF) Metarhizium anisopliae. The RPL23 gene fragment (414 bp) was cloned and phylogenetic analysis revealed that it’s very close to termite Coptotermes formosanus. Expression of RPL23 gene was significantly higher in abdomen as compared to thorax and head. Silencing RPL23 gene had no significant impact on the frequency and time of allogrooming towards fungus exposed termites from nestmates, which showed that nestmates acquired spores from infected termites through allogrooming. Expression of immune genes (GNBP1, GNBP2 and phenoloxidase) and apoptosis related genes (TNF-α, caspase 1, caspase 3 and caspase 8) decreased significantly in nestmates of fungus-treated termites after silencing of RPL23 gene as compared to control. Antifungal activity and survival of RPL23 silenced nestmates of fungus-treated termites also decreased. To sum up, this study found that silencing of RPL23 gene broke the active immunity against M. anisopliae infection, reduced the antifungal activity of termites, weakened cell apoptosis, and led to increased mortality of termites, which may help to find a potential alternative for chemical insecticides to control termites.

Biogenic silver nanoparticles synthesized using bracken fern inhibits cell proliferation in HCT-15 cells through induction of apoptosis pathway and overexpression of heat shock proteins

BackgroundIn recent years, biosynthesized nanoparticles has shown a promise as alternative avenue for improving the effectiveness of conventional chemotherapy. Despite, there is a significant gap in existing literature concerning the comprehensive study of biogenic silver nanoparticles derived from terrestrial fern species and their potential effects on cancer cells. This study is aiming to investigate effects of biogenic silver nanoparticles synthesized using aqueous extract of bracken fern Pteridium revolutum on inhibiting cell proliferation and inducing apoptosis in HCT-15 cells. MethodsBiogenic silver nanoparticles synthesized using aqueous extract of Pteridum revolutum followed by their characterization (UV–Visible spectroscopy, TEM, XRD and FTIR). The impact on cell proliferation of HCT-15 cells was assessed by MTT assay while induction of apoptosis was demonstrated via DNA fragmentation, caspase-3 assay, cell cycle arrest, FITC V- Annexin assay and evaluation of expression of apoptotic genes using real time PCR and western blotting techniques. ResultsResults of UV–Vis spectrum of colloidal solution of CW-AgNPs showed surface plasmon resonance peak at 430 nm. TEM and XRD results confirmed synthesis of spherical shaped, 20–40 nm sized nanoparticles. The results elucidate cytotoxic effect of PR-AgNPs against HCT-15 cells in time and dose dependent manner with IC50 observed at 5.79 ± 0.58 µg /mL after 24 h of exposure. Furthermore, PR-AgNPs induce significant alterations in cellular morphology, elevate DNA DNA fragmentation and enhance expression of p53 and caspase-3 in HCT10 cells. ConclusionThe findings from this study address the noteworthy antiproliferative effects of PR-AgNPs in cancer cells primarily mediated through activation of intrinsic apoptosis pathway by inducing p53 and caspase-3 genes.

Evolutionary dynamics of pro-inflammatory caspases in primates and rodents.

Caspase-1 and related proteases are key players in inflammation and innate immunity. Here, we characterize the evolutionary history of caspase-1 and its close relatives across 19 primates and 21 rodents, focusing on differences that may cause discrepancies between humans and animal studies. While caspase-1 has been retained in all these taxa, other members of the caspase-1 subfamily (caspase-4, -5, -11, -12, and CARD16, 17, and 18) each have unique evolutionary trajectories. Caspase-4 is found across simian primates, whereas we identified multiple pseudogenization and gene loss events in caspase-5, caspase-11, and the CARDs. Because caspases-4 and -11 are both key players in the non-canonical inflammasome pathway, we expected that these proteins would be likely to evolve rapidly. Instead, we found that these two proteins are largely conserved, whereas caspase-4's close paralog, caspase-5, showed significant indications of positive selection, as did primate caspase-1. Caspase-12 is a non-functional pseudogene in humans. We find this extends across most primates, although many rodents and some primates retain an intact, and likely functional, caspase-12. In mouse laboratory lines, we found that 50% of common strains carry non-synonymous variants that may impact the functions of caspase-11 and -12, and therefore recommend specific strains to be used (and avoided). Finally, unlike rodents, primate caspases have undergone repeated rounds of gene conversion, duplication, and loss leading to a highly dynamic pro-inflammatory caspase repertoire. Thus we uncovered many differences in the evolution of primate and rodent pro-inflammatory caspases, and discuss the potential implications of this history for caspase gene functions.