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Background and purpose: Excitotoxicity in nerve cells is a type of neurotoxicity in which excessive stimulation of receptors (such as N-methyl-d-aspartate glutamate receptors (NMDAR)) leads to the influx of high-level calcium ions into cells and finally cell damage or death. This complication can occur after taking some of the plasminogen activators like tissue plasminogen activator and reteplase. The interaction of the kringle2 domain in such plasminogen activator with the amino-terminal domain (ATD) of the NR1 subunit of NMDAR finally leads to excitotoxicity. In this study, we assessed the interaction of two new chimeric reteplase, mutated in the kringle2 domain, with ATD and compared the interaction of wild-type reteplase with ATD, computationally. Experimental approach: Homology modeling, protein docking, molecular dynamic simulation, and molecular dynamics trajectory analysis were used for the assessment of this interaction. Findings/Results: The results of the free energy analysis between reteplase and ATD (wild reteplase: -2127.516 ± 0.0, M1-chr: -1761.510 ± 0.0, M2-chr: -521.908 ± 0.0) showed lower interaction of this chimeric reteplase with ATD compared to the wild type. Conclusion and implications: The decreased interaction between two chimeric reteplase and ATD of NR1 subunit in NMDAR which leads to lower neurotoxicity related to these drugs, can be the start of a way to conduct more tests and if the results confirm this feature, they can be considered potential drugs in acute ischemic stroke treatment. [ABSTRACT FROM AUTHOR]

Locals in the Persian Gulf islands traditionally use Sinularia compressa to treat cancer. Therefore, this study deals with the cytotoxic activity of the soft coral Sinularia compressa chloroform extract (SCE), its pro-apoptotic activity, and the determination of its secondary metabolites. Cytotoxicity was done against MCF-7 and MDA-MB-231 and MCF‑10A cells. Apoptosis induction was checked by flow cytometry. The DCFDA and JC‐1 probes were used to assess the production of reactive oxygen species (ROS) and the mitochondrial transmembrane potential. Caspase-9, Bax, and Bcl-2 proteins were determined with ELISA Kit, and by western blot analysis. SCE exhibited cytotoxic activity with an IC50 value of 32.51 ± 0.70 μg/ml against MCF-7, and 8.53 ± 0.97 μg/ml against MDA-MB-231 cancer cells. The induction of the intrinsic apoptosis pathway was found by ROS generation, attenuation of Bcl-2 and induction of Bax proteins. It was supported by activation of caspase-9, increased apoptotic cells, as well as decrease of ΔΨm. In the acute toxicity, there was no detectable sign of hepatic or renal toxicity in the SCE 100 mg/kg. GC mass and NMR identified bioactive compounds as one monoterpene, one sesquiterpene, five fatty acids, one phthalate, and two steroidal compounds. [ABSTRACT FROM AUTHOR]

Neonatal hypoxic-ischemic (HI) brain injury is one of the major drawbacks of mortality and causes significant short/long-term neurological dysfunction in newborn infants worldwide. To date, due to multifunctional complex mechanisms of brain injury, there is no well-established effective strategy to completely provide neuroprotection. Although therapeutic hypothermia is the proven treatment for hypoxic-ischemic encephalopathy (HIE), it does not completely chang outcomes in severe forms of HIE. Therefore, there is a critical need for reviewing the effective therapeutic strategies to explore the protective agents and methods. In recent years, it is widely believed that there are neuroprotective possibilities of natural compounds extracted from plants against HIE. These natural agents with the anti-inflammatory, anti-oxidative, anti-apoptotic, and neurofunctional regulatory properties exhibit preventive or therapeutic effects against experimental neonatal HI brain damage. In this study, it was aimed to review the literature in scientific databases that investigate the neuroprotective effects of plant extracts/plant-derived compounds in experimental animal models of neonatal HI brain damage and their possible underlying molecular mechanisms of action. [ABSTRACT FROM AUTHOR]

Background: Autophagy plays a crucial role in modulating the proliferation of cancer diseases. However, the application of Naringenin (Nar), a compound with potential benefits against these diseases, has been limited due to its poor solubility and bioavailability., Objective: This study aimed to develop solid lipid nanoparticles (Nar-SLNs) loaded with Nar to enhance their therapeutic impact., Methods: In vitro experiments using Rin-5F cells exposed to Nar and Nar-SLNs were carried out to investigate the protective effects of Nar and its nanoformulation against the pancreatic cancer cell line of Rin-5F., Results: Treatment with Nar and Nar-SLN led to an increase in autophagic markers (Akt, LC3, Beclin1, and ATG genes) and a decrease in the level of miR-21. Both Nar and Nar-SLN treatments inhibited cell proliferation and reduced the expression of autophagic markers. Notably, Nar-SLNs exhibited greater efficacy compared to free Nar., Conclusion: These findings suggest that SLNs effectively enhance the cytotoxic impact of Nar, making Nar-SLNs a promising candidate for suppressing or preventing Rin-5F cell growth., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Gout, characterized by elevated uric acid levels, is a common inflammatory joint disease associated with pain, joint swelling, and bone erosion. Existing treatments for gout often result in undesirable side effects, highlighting the need for new, safe, and cost-effective anti-gout drugs. Natural products, including medicinal plants and phytochemicals, have gained attention as potential sources of anti-gout compounds. In this review, we examined articles from 2000 to 2020 using PubMed and Google Scholar, focusing on the effectiveness of medicinal plants and phyto-chemicals in managing gout. Our findings identified 14 plants and nine phytochemicals with anti-gout properties. Notably, Teucrium polium, Prunus avium, Smilax riparia, Rhus coriaria, Foenic-ulum vulgare, Allium cepa, Camellia japonica , and Helianthus annuus exhibited the highest xa-thine oxidase inhibitory activity, attributed to their unique natural bioactive compounds such as phenolics, tannins, coumarins, terpenoids, and alkaloids. Herbal plants and their phytochemicals have demonstrated promising effects in reducing serum urate and inhibiting xanthine. This review aims to report recent studies on plants/phytochemicals derived from herbs beneficial in gout and their different mechanisms., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)