The intention of this Special Issue is to elucidate the role of apoptosis and cellular senescence in different pathological processes, such as cancer and aging ....
Aging and neurodegenerative diseases share common hallmarks, including mitochondrial dysfunction and protein aggregation. Moreover, one of the major issues of the demographic crisis today is related ...to the progressive rise in costs for care and maintenance of the standard living condition of aged patients with neurodegenerative diseases. There is a divergence in the etiology of neurodegenerative diseases. Still, a disturbed endogenous pro-oxidants/antioxidants balance is considered the crucial detrimental factor that makes the brain vulnerable to aging and progressive neurodegeneration. The present review focuses on the complex relationships between oxidative stress, autophagy, and the two of the most frequent neurodegenerative diseases associated with aging, Alzheimer's disease (AD) and Parkinson's disease (PD). Most of the available data support the hypothesis that a disturbed antioxidant defense system is a prerequisite for developing pathogenesis and clinical symptoms of ADs and PD. Furthermore, the release of the endogenous hormone melatonin from the pineal gland progressively diminishes with aging, and people's susceptibility to these diseases increases with age. Elucidation of the underlying mechanisms involved in deleterious conditions predisposing to neurodegeneration in aging, including the diminished role of melatonin, is important for elaborating precise treatment strategies for the pathogenesis of AD and PD.
The hallmark of aging is an organism's difficulty to maintain proper homeostasis, leading to a disrupted balance between the endogenous antioxidant system and the production of free radicals, a ...progressive inflammatory process, and increased susceptibility to (neurodegenerative diseases ....
Endothelial cells are constantly exposed to environmental stress factors that, above a certain threshold, trigger cellular senescence and apoptosis. The altered vascular function affects new vessel ...formation and endothelial fitness, contributing to the progression of age-related diseases. This narrative review highlights the complex interplay between senescence, oxidative stress, extracellular vesicles, and the extracellular matrix and emphasizes the crucial role of angiogenesis in aging and Alzheimer's disease. The interaction between the vascular and nervous systems is essential for the development of a healthy brain, especially since neurons are exceptionally dependent on nutrients carried by the blood. Therefore, anomalies in the delicate balance between pro- and antiangiogenic factors and the consequences of disrupted angiogenesis, such as misalignment, vascular leakage and disturbed blood flow, are responsible for neurodegeneration. The implications of altered non-productive angiogenesis in Alzheimer's disease due to dysregulated Delta-Notch and VEGF signaling are further explored. Additionally, potential therapeutic strategies such as exercise and caloric restriction to modulate angiogenesis and vascular aging and to mitigate the associated debilitating symptoms are discussed. Moreover, both the roles of extracellular vesicles in stress-induced senescence and as an early detection marker for Alzheimer's disease are considered. The intricate relationship between endothelial senescence and angiogenesis provides valuable insights into the mechanisms underlying angiogenesis-related disorders and opens avenues for future research and therapeutic interventions.
Herein we pay attention to the design, synthesis and sensor activity of a novel biocompatible perylene-3,4,9,10-tetracarboxylic diimide (PDI) pH-probe in water. The synthesized compound shows ...selective fluorescence signalling properties as a function of pH (pKa value of 6.35 ± 0.02) which makes the probe suitable for pH determination in the physiological range. Thus prepared water soluble fluorescent system demonstrate low cytotoxicity to L929 cell lines from 330 μM to 1.3 μM and cell permeability in the lower concentration range. That findings show the high potential of the newly prepared PDI probe for monitoring of pH variations in bio-samples.
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•Fluorescent water-soluble perylene diimide pH probe is synthesized.•Probe is configured on the “fluorophore-spacer-receptor” model.•Probe operates via photoinduced electron transfer.•Probe shows low cytotoxicity towards L929 cell line.•Nano sized probe is cell-permeable at 0.001 mg/mL concentration.
Polyvinyl alcohol (PVA), a hydrophilic, biodegradable and biocompatible synthetic polymer, has been widely used in different areas of the biotechnological and biomedical field. PVA is very sensitive ...towards moisture and as a result the film strength is reduced, which is strongly undesirable for biomedical applications. To overcome this problem, new hybrid materials based on PVA and γ-aminopropyltriethoxyxilane (APTEOS), 3- mercaptopropyltriethoxysilane (MPTEOS) and tetraethoxysilane (TEOS) were prepared. Physisco-chemical surface characterization of the materials was done by measuring the water contact angle of the materials. The new materials were tested for potential use as matrices in tissue engineering application. Cytocompatibility and the cell adhesive behavior (actin cytoskeleton) of 3T3 cells as a function of surface functional groups were studied.
The synthesized PVA/APTEOS materials proved efficient for use in tissue engineering applications.
Synthesis of PVA/TEOS, PVA/APTEOS and PVA/MPTEOS hybrid matrices and adhesive behavior of 3T3 cells onto A) glass; B) PVA/TEOS; C) PVA/APTEOS; D) PVA/MPTEOS. Display omitted
► We synthesized novel hybrid materials based on PVA and APTEOS, 3- MPTEOS and TEOS. ► We characterized the surface of the PVA based hybrid materials. ► We studied the cytocompatibility and the cell adhesive behavior (actin cytoskeleton) of 3T3 cells.
(1) Background: The aim of the work is the evaluation of in vitro antiproliferative and pro-apoptotic activity of four benzimidazole derivatives containing colchicine-like and catechol-like moieties ...with methyl group substitution in the benzimidazole ring against highly invasive breast cancer cell line MDA-MB-231 and their related impairment of tubulin dynamics. (2) Methods: The antiproliferative activity was assessed with the MTT assay. Alterations in tubulin polymerization were evaluated with an in vitro tubulin polymerization assay and a docking analysis. (3) Results: All derivatives showed time-dependent cytotoxicity with IC50 varying from 40 to 60 μM after 48 h and between 13 and 20 μM after 72 h. Immunofluorescent and DAPI staining revealed the pro-apoptotic potential of benzimidazole derivatives and their effect on tubulin dynamics in living cells. Compound 5d prevented tubulin aggregation and blocked mitosis, highlighting the importance of the methyl group and the colchicine-like fragment. (4) Conclusions: The benzimidazole derivatives demonstrated moderate cytotoxicity towards MDA-MB-231 by retarding the initial phase of tubulin polymerization. The derivative 5d containing a colchicine-like moiety and methyl group substitution in the benzimidazole ring showed potential as an antiproliferative agent and microtubule destabilizer by facilitating faster microtubule aggregation and disrupting cellular and nuclear integrity.
We synthesized a series of novel indole compounds containing aroylhydrazone moieties and evaluated them in mice to check their anticonvulsant activity. In the present study the most potent ...C3-modified derivative
3e
, containing 2-furyl fragment was evaluated in kainate (KA)-induced status epilepticus (SE) and the consequences on oxidative stress and inflammation in the hippocampus in mice were explored. Melatonin was used as positive control while the melatonin receptor antagonist Luzindol was studied alone or in combination with melatonin or
3e
, respectively. After intraperitoneal (i.p.) pre-treatment with melatonin
3e
, Luzindol + melatonin and Luzindol +
3e
for 7 days (melatonin and
3e
—30 mg kg
−1
or 60 mg kg
−1
, Luzindol 10 mg kg
−1
) the animals were i.p. injected with KA (30 mg kg
−1
, i.p.). The
3e
decreased the SE-induced seizure intensity while melatonin suppressed seizures at the higher dose of 60 mg kg
−1
. Luzindol blocked the anticonvulsant effect of both Mel and
3e.
The dose-dependent antioxidant effect of
3e
measured by reduced glutathione (GSH) and total GSH in the hippocampus, was comparable to the effect of melatonin. Luzindol fully blocked the effect of melatonin but affected partially the antioxidant activity of
3e
. The KA-induced increased amplifier of neuroinflammation high-mobility group box protein 1 (HMGB1) was neither alleviated by melatonin, nor by
3e.
The activation by this DNA-binding protein receptor for advanced glycation end products (RAGE) was not affected by SE, melatonin and
3e
pre-treatment. Our results suggest that the novel indole derivate
3e
, containing 2-furyl fragment, might be clinically useful as an adjunct therapy against SE and concomitant oxidative stress.
The pineal gland regulates the aging process via the hormone melatonin. The present report aims to evaluate the effect of pinealectomy (pin) on behavioral and oxidative stress-induced alterations in ...cholesterol and sphingomyelin (SM) levels in young adult, mature and aging rats. Sham and pin rats aged 3, 14 and 18 months were tested in behavioral tests for motor activity, anxiety, and depression. The ELISA test explored oxidative stress parameters and SM in the hippocampus, while total cholesterol was measured in serum via a commercial autoanalyzer. Mature and aged sham rats showed low motor activity and increased anxiety compared to the youngest rats. Pinealectomy affected emotional responses, induced depressive-like behavior, and elevated cholesterol levels in the youngest rats. However, removal of the pineal gland enhanced oxidative stress by diminishing antioxidant capacity and increasing the MDA level, and decreased SM level in the hippocampus of 14-month-old rats. Our findings suggest that young adult rats are vulnerable to emotional disturbance and changes in cholesterol levels resulting from melatonin deficiency. In contrast, mature rats with pinealectomy are exposed to an oxidative stress-induced decrease in SM levels in the hippocampus.
One of the pathological hallmarks of Alzheimer’s disease (AD) associated with its progression that contributes to β-amyloid (Aβ) generation is oxidative stress (OS). Clinical data suggest that ...melatonin is a potent antioxidant that might be effective in the adjunctive therapy of this neurodegenerative disease. The present study aimed to explore the role of melatonin on behavioral changes and markers of OS in three rat models, namely, pinealectomy (pin) model of melatonin deficit, intracerebroventricular (icv)Aβ1-42 model of AD, and combination of both pin and Aβ1-42 model (pin+icvAβ1-42). The chronic injection with vehicle/melatonin (50 mg/kg, i.p. for 40 days) started on the same day of sham/pin and icv vehicle/Aβ1-42 infusion procedures. Anxiety in the open field and the elevated plus-maze test and cognitive responses in the object recognition test were tested between the 30th–35th day after the surgical procedures. Markers of OS in the frontal cortex (FC) and hippocampus were detected by the ELISA method. Melatonin treatment corrected the exacerbated anxiety response only in the pin+icvAβ1-42 model while it alleviated the cognitive impairment in the three models. Pinealectomy disturbed the antioxidant system via enhanced SOD activity and decreased GSH levels both in the FC and hippocampus. The Aβ1-42 model decreased the SOD activity in the FC and elevated the MDA level in the two brain structures. The pin+icvAβ1-42 model impaired the antioxidant system and elevated lipid peroxidation. Melatonin supplementation restored only the elevated MDA level of icvAβ1-42 and pin+icvAβ1-42 model in the hippocampus. In conclusion, our study reveals that the pin+icvAβ1-42 rat model triggers more pronounced anxiety and alterations in markers of OS that may be associated with melatonin deficit concomitant to icvAβ1-42-induced AD pathology.
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