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Background: Acute pancreatitis (AP) presents a significant clinical challenge with limited therapeutic options. The complex etiology and pathophysiology of AP emphasize the need for innovative treatments. This study explores mRNA-based therapies delivering fibroblast growth factor 21 (FGF21) and apolipoprotein A1 (APOA1), alone and in combination, for treating experimental AP. Methods: Liver-targeted lipid nanoparticles (LNP)-mRNA formulations encoding FGF21, APOA1, and a chimeric APOA1-FGF21, were first tested for protein expression and bioavailability in vitro and in mice fed a high-fat diet. Efficacy studies were performed in the caerulein-induced AP (Cer-AP) model, and a new AP model combining ethanol feeding with ethanol binge plus palmitoleic acid administration, the EtOH/POA-AP model. A single dose of the APOA1, FGF21, and APOA1-FGF21 LNP-mRNAs formulations was administered in both models. Serum levels of pancreatic lipase (LIPC), amylase (AMYL), and aspartate aminotransferase (AST), along with pancreatic tissue analyses using two histopathological scores were performed to evaluate treatment effects. Results: In vitro studies demonstrated the translation and secretion of APOA1, FGF21, and APOA1-FGF21 proteins encoded by the LNP-mRNAs. In vivo, LNP-mRNA administration increased serum levels of the respective proteins in metabolically impaired (i.e. high fat diet-fed) mice. In the Cer-AP model, serum markers of pancreatic injury were similarly reduced when mice were treated with APOA1, FGF21, and APOA1-FGF21 LNP-mRNA, and this effect was also observed in the histopathological analyses. The EtOH/POA-AP model was more aggressive than the Cer-AP model. FGF21 and APOA1-FGF21 LNP-mRNAs were protective according to LIPC and AMYL serum levels, while APOA1 LNP-mRNA had little effect. On the other hand, histological improvements were more evident in mice receiving APOA1 LNP-mRNA. In the EtOH/POA-AP model, FGF21 and APOA1-FGF21 LNP-mRNAs reduced serum AST levels, indicating hepatoprotective activity. Discussion: This proof-of-concept study demonstrates the potential of mRNA-based therapies delivering FGF21 and APOA1 in experimental AP. While individual treatments effectively reduced pancreatic injury, the APOA1-FGF21 fusion molecule did not exhibit superior activity. Liver-targeted LNP-mRNA administration may offer a promising approach for treating AP, leveraging endogenous production pathways for therapeutic proteins. Further research is warranted to elucidate the mechanisms underlying their therapeutic efficacy and optimize treatment regimens for clinical translation. [ABSTRACT FROM AUTHOR]

Background: (-)-Fenchone is a bicyclic monoterpene present in the plant species Foeniculum vulgare Mill, Thuja occidentalis L. (tuja), and Lavandula stoechas (lavender). These plants have therapeutic value in the treatment of intestinal disorders. Aim: To evaluate intestinal anti-inflammatory activity in an acute and chronic trinitrobenzene sulphonic acid (TNBS)-induced colitis model in rats. Methods: Intestinal anti-inflammatory effects were assessed using the acute and chronic TNBS-induced colitis model in rats. The mechanisms were evaluated from colonic tissue fragments of the acute and chronic models. Results: Oral administration of the (-)-fenchone (37.5–300 mg/kg) acute phase or (150 mg/kg) (p < 0.001) chronic phase reduced the macroscopic lesion score, ulcerative area, intestinal weight/length ratio, and diarrheal index in TNBS-treated animals. At a dose of 150 mg/kg, the acute and chronic phase decreased malondialdehyde (MDA) and myeloperoxidase (MPO) (p < 0.001), restored glutathione (GSH) levels and superoxide dismutase (SOD) (p < 0.001), decreased immunomarking for factor nuclear kappa B (NF-κB) and levels of interleukin (IL)-1 and tumor necrosis factor α (TNF-α), and maintained IL-10 and TGF-β basal levels. Furthermore, increased immunostaining for zonula occludens 1 (ZO-1) was observed. Conclusions: (-)-fenchone has intestinal anti-inflammatory activity related to cytoprotection of the intestinal barrier, as well as antioxidant and immunomodulatory effects. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) are the leading cause of death worldwide, and effectively repairing the heart following myocardial injuries remains a significant challenge. Research has increasingly shown that exosomes derived from mesenchymal stem cells (MSC-Exo) can ameliorate myocardial injuries and improve outcomes after such injuries. The therapeutic benefits of MSC-Exo are largely due to their capacity to deliver specific cargo, including microRNAs and proteins. MSC-Exo can modulate various signaling pathways and provide several beneficial effects, including cytoprotection, inflammation modulation, and angiogenesis promotion to help repair the damaged myocardium. In this review, we summarize the cardioprotective effects of MSC-Exo in myocardial injury, the underlying molecular mechanism involved in the process, and various approaches studied to enhance their efficacy based on recent findings. [ABSTRACT FROM AUTHOR]

An ischemic cerebral stroke results from the interruption of blood flow to the brain, triggering rapid and complex cascades of excitotoxicity, oxidative stress, and inflammation. Current reperfusion therapies, including intravenous thrombolysis and mechanical thrombectomy, cause further brain injury due to reperfusion-induced cytotoxicity. To date, novel cytoprotective therapies that could address these challenges have yet to be developed, likely due to the limitations of targeting a single pathologic mechanism. To address these unmet clinical needs, we investigated a synthetic verbenone derivative, SP-8356, as a potential multi-target cytoprotective agent for acute ischemic strokes. In transient middle cerebral artery occlusion (MCAO) rats, SP-8356 significantly reduced brain infarct and edema volumes while improving acute neurological deficits in a dose-dependent manner. Furthermore, SP-8356 improved long-term outcomes, particularly by reducing mortality. These potent cytoprotective effects of SP-8356 were achieved by suppressing the excessive production of free radicals and pro-inflammatory cytokines, reducing the infiltration of inflammatory cells, and mitigating increases in blood–brain barrier permeability. Additional research is needed to determine whether co-administration of SP-8356 can extend the therapeutic time window of reperfusion therapies by mitigating ischemia/reperfusion injury. [ABSTRACT FROM AUTHOR]

Macroautophagy, commonly referred to as autophagy, is an essential cytoprotective mechanism that plays a significant role in cellular homeostasis. It has emerged as a promising target for drug development aimed at treating various cancers and infectious diseases. However, the scientific community has yet to reach a consensus on the most effective approach to manipulating autophagy, with ongoing debates about whether its inhibition or stimulation is preferable for managing these complex conditions. One critical factor contributing to the variability in treatment responses for both cancers and infectious diseases is estrogen, a hormone known for its diverse biological effects. Given the strong correlations observed between estrogen signaling and autophagy, this review seeks to summarize the intricate molecular mechanisms that underlie the dual cytoprotective effects of estrogen signaling in conjunction with autophagy. We highlight recent findings from studies that involve various ligands, disease contexts, and cell types, including immune cells. Furthermore, we discuss several factors that regulate autophagy in the context of estrogen's influence. Ultimately, we propose a hypothetical model to elucidate the regulatory effects of the estrogen–autophagy axis on cell fate. Understanding these interactions is crucial for advancing our knowledge of related diseases and facilitating the development of innovative treatment strategies. [ABSTRACT FROM AUTHOR]

Viral infections and many other dangerous diseases are accompanied by the development of oxidative stress, which is a consequence of an increase in the level of the reactive oxygen species (ROS). In this regard, the search for effective antioxidants remains highly relevant. We tested fullerenol C60(OH)36 in the context of the connection between its self-assembly in aqueous solutions and cell culture media, antiradical activity, UV cytoprotective action, and antiviral activity against international reference strains of influenza virus A(H1N1)pdm09, A(H3N2), and B subtypes in vitro on the MDCK cell line. Various characterization techniques, including Fourier-transform infrared spectroscopy (FTIR), Raman spectroscopy, NMR and ESR spectrometry, MALDI-TOF mass spectrometry, thermal analysis (TGA and DSC), dynamic light-scattering (DLS), and ζ-potential measurements, were used to confirm the production of fullerenol and study its self-assembly in aqueous solutions and cell culture media. Fullerenol C60(OH)36 demonstrated the ability to scavenge •DPPH, •OH, O2•− radicals and 1O2 and was non-toxic in the range of the studied concentrations (up to 200 μg/mL) when incubated with MDCK cells for 24 h. In addition, fullerenol exhibited a cytoprotective effect under UV irradiation (EC50 = 29.7 ± 1.0 μM) and showed moderate activity against human influenza viruses of subtypes A(H1N1)pdm09 (SI = 9.9 ± 4.6) and A(H3N2) (SI = 12.5 ± 1.3) when determined by the hemagglutination assay (HA-test) and the MTT assay. At the same time, C60(OH)36 was ineffective in vitro against the actual strain of influenza B virus (Victoria lineage). The high bioavailability of fullerenol in combination with its cytoprotective effect, as well as its antiradical and antiviral activity combined with a relatively low toxicity, allows to consider it a promising compound for biomedical applications. [ABSTRACT FROM AUTHOR]

Abstract By inhibiting acetylcholinesterase (AChE) activity, organophosphate compounds (OPs) can quickly cause severe injury to the nervous system and death, making it extremely difficult to rescue victims after OP exposure. However, it is quite challenging to construct scavengers that neutralize and eliminate these harmful chemical agents promptly in the blood circulation system. Herein, we report an enzyme-armed biomimetic nanoparticle that enables a ‘targeted binding and catalytic degradation’ action mechanism designed for highly efficient in vivo detoxification (denoted as ‘Nanocleaner’). Specifically, the resulting Nanocleaner is fabricated with polymeric cores camouflaged with a modified red blood cell membrane (RBC membrane) that is inserted with the organophosphorus hydrolase (OPH) enzyme. In such a subtle construct, Nanocleaner inherits abundant acetylcholinesterase (AChE) on the surface of the RBC membrane, which can specifically lure and neutralize OPs through biological binding. The OPH enzyme on the membrane surface breaks down toxicants catalytically. The in vitro protective effects of Nanocleaner against methyl paraoxon (MPO)-induced inhibition of AChE activity were validated using both preincubation and competitive regimens. Furthermore, we selected the PC12 neuroendocrine cell line as an experimental model and confirmed the cytoprotective effects of Nanocleaner against MPO. In mice challenged with a lethal dose of MPO, Nanocleaner significantly reduces clinical signs of intoxication, rescues AChE activity and promotes the survival rate of mice challenged with lethal MPO. Overall, these results suggest considerable promise of enzyme-armed Nanocleaner for the highly efficient removal of OPs for clinical treatment.

Glutamate-mediated excitotoxicity has been extensively explored as a therapeutic target for the development of potential treatments of neurological disorders including stroke. However, the effect of glutamate on astrocytes under pathological conditions has been less studied. Using primary astrocyte culture, we determined the effect of glutamate on astrocytes against ischemic insult. Glutamate provided a cytoprotective effect and acted as an alternative substrate for ATP production in primary astrocytes against oxygen glucose deprivation reoxygenation insult, which was blocked by glutamate uptake inhibition. The cytoprotective effect of glutamate appears to be astrocyte-specific, as glutamate dose-dependently induces cytotoxic action in murine hippocampal HT-22 cell line. Interestingly, the cytoprotective effect of glutamate against glucose deprivation was short-last, as no protection was observed after 3-day glucose deprivation. We determined the metabolic phenotype of primary astrocyte cultured in glucose or glutamate. Primary astrocytes cultured in glutamate displayed a different metabolic phenotype when compared to those cultured in glucose, evidenced by higher basal and maximal oxygen consumption rate (OCR), higher ATP production and proton leak-coupled OCR, as well as lower glycolysis. Furthermore, glutamate exposure resulted in astrocyte activation, evidenced by an increase in astrocyte size and GFAP expression. Our study demonstrated that glutamate exerts a dual effect on astrocytes under ischemic condition. Glutamate provides an alternative substrate for energy metabolism in the absence of glucose, thereby protecting astrocytes against ischemic insults. On the other hand, glutamate exposure induces astrogliosis. Modulation of glutamate uptake and metabolism in astrocytes may provide novel targets for alleviating ischemic injury and improving function recovery after ischemic stroke. [ABSTRACT FROM AUTHOR]

Oenobiol Sun Expert, a food formulation designed to enhance skin health prior to sun exposure, has been optimized by incorporating the OenoGrape Advanced Complex, which includes grape pomace extract, increased selenium content and 10% lycopene-rich tomato extract, with these constituents exhibiting high antioxidant potential. To evaluate the effects of these individual ingredients and the overall formulation at the cellular level, the AOP1 cell antioxidant efficacy assay was employed to measure the intracellular free radical scavenging activity, while the Cell Antioxidant Assay (CAA or DCFH-DA) assay was used to assess peroxidation scavenging at the plasma membrane level. The indirect antioxidant activity was examined using stably transfected cell lines containing a luciferase reporter gene controlled by the Antioxidant Response Element (ARE), which activates the endogenous antioxidant system via the Nrf2/Keap1-ARE pathway. Our results indicate that among the individual components, grape pomace extract and sodium selenite possess high and complementary antioxidant properties. Grape pomace extract was particularly effective in inhibiting free radicals (AOP1 EC50 = 6.80 μg/mL) and activating the ARE pathway (ARE EC50 = 231.1 μg/mL), whereas sodium selenite exerted its effects through potent ARE activation at sub-microgram levels (EC50 = 0.367 μg/mL). In contrast, the lycopene-rich tomato extract did not show a notable contribution to the antioxidant effects. The antiradical activity of the OenoGrape Advanced Complex, comprising these three ingredients, was very efficient and consistent with the results obtained for the individual components (AOP1 EC50 = 15.78 µg/mL and ARE EC50 of 707.7 μg/mL). Similarly, the free radical scavenging activity still persisted in the Oenobiol Sun Expert formulation (AOP1 EC50 = 36.63 µg/mL). Next, in vitro intestinal transepithelial transfer experiments were performed. The basolateral compartments of cells exposed to the ingredients were collected and assessed using the same antioxidant cell assays. The direct and indirect antioxidant activities were measured on both hepatocytes and keratinocytes, demonstrating the bioavailability and bioactivity of grape pomace extract and sodium selenite. These finding suggest that the ingredients of this food supplement contribute to enhanced cytoprotection following ingestion. [ABSTRACT FROM AUTHOR]

Numerous beneficial effects of resveratrol were reported; however, its pharmacological profile is contradictious. Previously, we have demonstrated that resveratrol has a dose-dependent cytoprotective effect and the essential role of autophagy induction was demonstrated. Resveratrol suffers from unfavorable pharmacokinetics, hindering its clinical use. Our aim was to study the cytoprotective effect of resveratrol derivatives to better understand structure–activity relationships that may facilitate the development of compounds with better druglike characteristics. Serum-deprivation-induced caspase activation, free radical generation, mitochondrial membrane depolarization and autophagy were detected in the presence of resveratrol analogs with different oxidation states on mouse embryonal fibroblasts. Distinct cytoprotective mechanisms of the examined compounds were revealed. Monomethyl resveratrol had similar potency to resveratrol (EC50: 85.3 vs. 84.2 μM); however, autophagy induction was not essential for its cytoprotective effect. Oxyresveratrol was found to be a strong antioxidant that can induce direct cytoprotection rather than autophagy. Trimethyl-resveratrol, lacking free hydroxyl groups, induced damage that was too significant and hardly compensated by the activation of cytoprotective machineries, and caspase activation was reduced by only 24.5%. Based on our results, methylation of resveratrol reduces its antioxidant activity, while autophagy induction can still contribute to its cytoprotective effect. The introduction of an additional hydroxyl group, however, augments the antioxidant properties, inducing cytoprotection without autophagy induction. [ABSTRACT FROM AUTHOR]

Protective effect of quercetin against acetaldehyde was evaluated using the cultured hepatocyte models with aldehyde dehydrogenase (ALDH) isozyme deficiency (aldh2-kd and aldh1a1-kd). The quercetin-induced cytoprotection against acetaldehyde in the ALDH1A1-deficient mutant (aldh1a1-kd) was weaker than that in the wild type. Furthermore, quercetin did not enhance the ALDH activity in aldh1a1-kd cells, suggesting that ALDH1A1 is involved in quercetin-induced cytoprotection. [ABSTRACT FROM AUTHOR]

Since the early 1990s, when Robert's and Szabo's cytoprotection concept had already been more than one decade old, but still not implemented in therapy, we suggest the stable gastric pentadecapeptide BPC 157 as the most relevant mediator of the cytoprotection concept. Consequently, it can translate stomach and gastrointestinal mucosal maintenance, epithelium, and endothelium cell protection to the therapy of other tissue healing (organoprotection), easily applicable, as native and stable in human gastric juice for more than 24 h. These overwhelm current clinical evidence (i.e., ulcerative colitis, phase II, no side effects, and no lethal dose (LD1) in toxicology studies), as BPC 157 therapy effectively combined various tissue healing and lesions counteraction. BPC 157 cytoprotection relevance and vascular recovery, activation of collateral pathways, membrane stabilizer, eye therapy, wound healing capability, brain–gut and gut–brain functioning, tumor cachexia counteraction, muscle, tendon, ligament, and bone disturbances counteraction, and the heart disturbances, myocardial infarction, heart failure, pulmonary hypertension, arrhythmias, and thrombosis counteraction appeared in the recent reviews. Here, as concept resolution, we review the counteraction of advanced Virchow triad circumstances by activation of the collateral rescuing pathways, depending on injury, activated azygos vein direct blood flow delivery, to counteract occlusion/occlusion-like syndromes starting with the context of alcohol-stomach lesions. Counteraction of major vessel failure (congested inferior caval vein and superior mesenteric vein, collapsed azygos vein, collapsed abdominal aorta) includes counteraction of the brain (intracerebral and intraventricular hemorrhage), heart (congestion, severe arrhythmias), lung (hemorrhage), and congestion and lesions in the liver, kidney, and gastrointestinal tract, intracranial (superior sagittal sinus), portal and caval hypertension, aortal hypotension, and thrombosis, peripherally and centrally. [ABSTRACT FROM AUTHOR]

We studied the radical-binding and antioxidant activities of the alkaloid tryptanthrin (TR) and its new synthetic derivative tryptanthrin oxime (TR-Ox), as well as the cytoprotective activity of TR-Ox under conditions of oxidative stress. The antiradical activity of TR-Ox was revealed in the test of binding with stable chromogen radical 2,2-diphenyl-1-picrylhydrazyl and in the superoxide radical generation test (riboflavin photoreduction reaction with detection by NBT reduction). TR-Ox was inferior to ionol and dihydroquercetin by the antiradical activity. In these tests, TR did not exhibit antiradical activity. TR-Ox did not show iron-chelating activity (in the test with the formation of the o-phenanthroline-Fe2+ complex and its destruction in the presence of chelating agents). In brain homogenate, TR-Ox significantly reduced the increase in spontaneous chemiluminescence. Under conditions of oxidative stress induced by 15 mM H2O2 in the SH-SY5Y neuroblastoma cell culture, TR-Ox exhibited cytoprotective activity and increased the number of viable cells. [ABSTRACT FROM AUTHOR]

The Great Salt Lake, located in Utah, USA, is a saltwater lake with no outlet and is surrounded by vast mountains and salt deserts. We aimed to use Great Salt Lake-derived processed mineral water (hereafter termed as GSL-MW) for maintaining oral health. Therefore, we examined its radical scavenging activity as an antioxidant and its cytoprotective effect on human gingival fibroblasts (hGFs). The scavenging activity against O2•− radicals was determined by an electron spin resonance (ESR)-spin trapping technique using two kinds of O2•− generation systems; however, we could not reach any concrete conclusion because of the interference caused by GSL-MW in both systems. Detection of ·OH radicals using the ESR-spin trapping technique and kinetic analyses using double-reciprocal plots (corresponding to Lineweaver–Burk plots that are used to represent enzyme kinetics) revealed that GSL-MW has the ability to scavenge ·OH radicals. GSL-MW also showed a weak 2,2-diphenyl-1-picrylhydrazyl (DPPH; a stable radical)-scavenging activity. Regarding the cytoprotective effects, subconfluent hGFs pretreated with 10× and 100× dilutions of GSL-MW for 3 min and then exposed to harsh environmental conditions, such as pure water or 100 μM H2O2 for 3 min, showed enhanced cell viability rate. Moreover, 10× and 100× dilutions of GSL-MW reduced oxidative damage in confluent hGFs exposed to 12.5 and 25 mM H2O2. Our findings show that GSL-MW has antioxidant potential and cytoprotective effects on hGFs, suggesting that GSL-MW can be used to maintain oral health. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disease with complex pathogenesis. Despite the pathogenesis is unknown, the misfolding and accumulation of β-amyloid (Aβ) peptide play the important role in the occurrence and development of AD. Hence, multi-aspect intervention of the misfolded Aβ peptides aggregation is a promising therapy for AD. In previous work, we obtained the emodin derivatives (a–d) with multifunctional anti-AD activities, including metal ions chelation, cholinesterase inhibition, and hydroxyl/superoxide anion radical elimination. In this work, we predicted the interaction of emodin derivatives (a–d) with Aβ by combining molecular docking simulation and molecular dynamics simulation, and evaluated the ability to intervene with the self-, Cu2+- and AChE-induced Aβ aggregation via in vitro methods. The results indicated that a–d could act as the potent multi-aspect intervention agents for Aβ aggregation. In addition, a–d could effectively eliminate peroxyl radical, had virtually no neurotoxicity, and protect cells from oxidative and Aβ-induced damage. The prediction results of ADMET properties showed that a–d had suitable pharmacokinetic characteristics. It suggested that a–d could act as the promising multi-targeted directed ligands (MTDLs) for AD. These results may provide meaningful information for the development of the potential MTDLs for AD which are modified from natural-origin scaffolds. [ABSTRACT FROM AUTHOR]

By inhibiting acetylcholinesterase (AChE) activity, organophosphate compounds (OPs) can quickly cause severe injury to the nervous system and death, making it extremely difficult to rescue victims after OP exposure. However, it is quite challenging to construct scavengers that neutralize and eliminate these harmful chemical agents promptly in the blood circulation system. Herein, we report an enzyme-armed biomimetic nanoparticle that enables a 'targeted binding and catalytic degradation' action mechanism designed for highly efficient in vivo detoxification (denoted as 'Nanocleaner'). Specifically, the resulting Nanocleaner is fabricated with polymeric cores camouflaged with a modified red blood cell membrane (RBC membrane) that is inserted with the organophosphorus hydrolase (OPH) enzyme. In such a subtle construct, Nanocleaner inherits abundant acetylcholinesterase (AChE) on the surface of the RBC membrane, which can specifically lure and neutralize OPs through biological binding. The OPH enzyme on the membrane surface breaks down toxicants catalytically. The in vitro protective effects of Nanocleaner against methyl paraoxon (MPO)-induced inhibition of AChE activity were validated using both preincubation and competitive regimens. Furthermore, we selected the PC12 neuroendocrine cell line as an experimental model and confirmed the cytoprotective effects of Nanocleaner against MPO. In mice challenged with a lethal dose of MPO, Nanocleaner significantly reduces clinical signs of intoxication, rescues AChE activity and promotes the survival rate of mice challenged with lethal MPO. Overall, these results suggest considerable promise of enzyme-armed Nanocleaner for the highly efficient removal of OPs for clinical treatment. [ABSTRACT FROM AUTHOR]

This work provides insight into carbamazepine polymorphs (Forms I, II, III, IV, and V), with reports on the cytoprotective, exploratory, motor, CNS-depressant, and anticonvulsant properties of carbamazepine (CBZ), carbamazepine formulation (CBZ-F), topiramate (TOP), oxcarbazepine (OXC), and diazepam (DZP) in mice. Structural analysis highlighted the significant difference in molecular conformations, which directly influence the physicochemical properties; and density functional theory description provided indications about CBZ reactivity and stability. In addition to neuron viability assessment in vitro, animals were treated orally with vehicle 10 mL/kg, as well as CBZ, CBZ-F, TOP, OXC, and DZP at the dose of 5 mg/kg and exposed to open-field, rotarod, barbiturate sleep induction and pentylenetetrazol (PTZ 70 mg/kg)-induced seizure. The involvement of GABAergic mechanisms in the activity of these drugs was evaluated with the intraperitoneal pretreatment of flumazenil (2 mg/kg). The CBZ, CBZ-F, and TOP mildly preserved neuronal viability. The CBZ-F and the reference AEDs potentiated barbiturate sleep, altered motor activities, and attenuated PTZ-induced convulsion. However, flumazenil pretreatment blocked these effects. Additional preclinical assessments could further establish the promising utility of CBZ-F in clinical settings while expanding the scope of AED formulations and designs. [ABSTRACT FROM AUTHOR]

Copyright of Hungarian Medical Journal / Orvosi Hetilap is the property of Akademiai Kiado and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

缺血性卒中是致死致残的重症疾病之一。缺血性卒中患者预后不理想的重要原因之一是缺血级联反应造成的脑组织损伤。因此，积极的脑细胞保护治疗对改善缺血性卒中的预后至关重要。近年来，国内外大量临床前和临床研究证据层出不穷。基于更多新治疗靶点的涌现以及更多治疗方式的突破，结合最新卒中治疗学术产业圆桌会议的内容，本声明对缩小目前缺血性卒中研究临床转化鸿沟的探索、脑细胞保护的临床研究，以及如何有助于实现更多治疗方式的临床转化做一科学声明，旨在推进缺血性卒中脑细胞保护临床前及临床研究的开展，进一步改善缺血性卒中患者的临床预后。 Abstract: Ischemic stroke is one of the serious diseases that cause death and disability. One of the important reasons for the unsatisfactory prognosis of patients with ischemic stroke is the damage to brain tissue resulting from the ischemic cascade reaction. Therefore, active brain cytoprotection therapy is essential for ischemic stroke treatment. In recent years, evidence from many preclinical studies and clinical research has emerged at home and abroad. With the emergence of new therapeutic targets and breakthroughs in treatment approaches, combined with the content of the latest Stroke Treatment Academic Industry Roundtable, this paper makes a scientific statement on the exploration of strategies to bridge the gap of clinical transformation in ischemic stroke, clinical research on brain cytoprotection, and how can exploration contribute to the clinical transformation of more treatment approaches. The objective is to promote the development of preclinical studies and clinical research in brain cytoprotection for ischemic stroke, and further improve the clinical prognosis of patients with ischemic stroke.

In this study, antioxidant peptides derived from sheep hemoglobin were prepared from fresh sheep blood. Sephadex G-25 chromatography, DEAE Sephadex A-50 chromatography, reverse phase high performance liquid chromatography (RP-HPLC) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to separate, purify, and identify peptides from the hydrolysate of sheep hemoglobin. The antioxidant activity of the obtained peptides was evaluated by their free radical scavenging capacity, stability against simulated gastrointestinal digestion and protective effect on H2O2-induced oxidative injury in Caco-2 cells. The results indicated that three novel antioxidant peptides, Ala-Tyr-Glu-Val-Asp (AYEVD), Phe-His-Thr-Met-Glu (FHTME) and Ser-Phe-Met-Tyr-Glu-Lys (SFMYEK), were purified and identified from the hydrolysate, with molecular masses of 595.60, 663.74 and 803.92 Da, respectively. Among them, AYEVD had the strongest scavenging capacity to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, and AYEVD showed stronger antioxidant activity after simulated gastrointestinal digestion. In addition, AYEVD inhibited H2O2-induced oxidative injury in Caco-2 cells, significantly reduced the accumulation of reactive oxygen species (ROS), suppressed early cell apoptosis and the formation of malondialdehyde (MDA), and increased the activity of intracellular antioxidant enzymes. Therefore, this study could provide a theoretical basis for the application of novel antioxidant peptides from sheep hemoglobin in functional foods.

It is still unclear whether or how quercetin influences the toxic events induced by acetaldehyde in hepatocytes, though quercetin has been reported to mitigate alcohol-induced mouse liver injury. In this study, we evaluated the modulating effect of quercetin on the cytotoxicity induced by acetaldehyde in mouse hepatoma Hepa1c1c7 cells, the frequently used cellular hepatocyte model. The pretreatment with quercetin significantly inhibited the cytotoxicity induced by acetaldehyde. The treatment with quercetin itself had an ability to enhance the total ALDH activity, as well as the ALDH1A1 and ALDH3A1 gene expressions. The acetaldehyde treatment significantly enhanced the intracellular reactive oxygen species (ROS) level, whereas the quercetin pretreatment dose-dependently inhibited it. Accordingly, the treatment with quercetin itself significantly up-regulated the representative intracellular antioxidant-related gene expressions, including heme oxygenase-1 (HO-1), glutamate-cysteine ligase, catalytic subunit (GCLC), and cystine/glutamate exchanger (xCT), that coincided with the enhancement of the total intracellular glutathione (GSH) level. Tin protoporphyrin IX (SNPP), a typical HO-1 inhibitor, restored the quercetin-induced reduction in the intracellular ROS level, whereas buthionine sulphoximine, a representative GSH biosynthesis inhibitor, did not. SNPP also cancelled the quercetin-induced cytoprotection against acetaldehyde. These results suggest that the low-molecular-weight antioxidants produced by the HO-1 enzymatic reaction are mainly attributable to quercetin-induced cytoprotection. [ABSTRACT FROM AUTHOR]

Background and Purpose: IL‐11 is a member of the IL‐6 family of cytokine initially considered as haematopoietic and cytoprotective factor. Recent evidence indicates that IL‐11 promotes lung fibrosis and pulmonary hypertension in animal models and is elevated in lung tissue of patients with pulmonary fibrosis and pulmonary hypertension. Fibrocytes are bone marrow‐derived circulating cells that participate in lung fibrosis and pulmonary hypertension, but the role of IL‐11 on fibrocytes is unknown. We investigated the role of IL‐11 system on fibrocyte activation in different in vitro and in vivo models of lung fibrosis associated with pulmonary hypertension. Experimental Approach: Human fibrocytes were isolated from peripheral blood of six healthy donors. Recombinant human (rh)‐IL‐11 and soluble rh‐IL‐11 receptor, α subunit (IL‐11Rα) were used to stimulated fibrocytes in vitro to measure:‐ cell migration in a chemotactic migration chamber, fibrocyte to endothelial cell adhesion in a microscope‐flow chamber and fibrocyte to myofibroblast transition. Mouse lung fibrosis and pulmonary hypertension was induced using either IL‐11 (s.c.) or bleomycin (intra‐tracheal), while in the rat monocrotaline (intra‐tracheal) was used. In vivo siRNA‐IL‐11 was administered to suppress IL‐11 in vivo. Key Results: RhIL‐11 and soluble rhIL‐11Rα promote fibrocyte migration, endothelial cell adhesion and myofibroblast transition. Subcutaneous (s.c.) IL‐11 infusion elevates blood, bronchoalveolar and lung tissue fibrocytes. SiRNA‐IL‐11 transfection in bleomycin and monocrotaline animal models reduces blood and lung tissue fibrocytes and reduces serum CXCL12 and CXCL12/CXCR4 lung expression. Conclusion and Implications: Targeting IL‐11 reduces fibrocyte circulation and lung accumulation in animal models of pulmonary hypertension‐associated lung fibrosis. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Stroke is the property of Chinese Journal of Stroke Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Na+/H+ exchanger type 1 (NHE-1) is a validated drug target for the treatment of cardiovascular and ophthalmic diseases due to the cytoprotective, anti-ischemic and anti-inflammatory properties of NHE-1 inhibitors. This article presents data on the synthesis and pharmacological activity studies of novel guanidine derivatives of quinazoline-2,4(1H,3H)-dione 6-11 and reference drugs amiloride, rimeporide, zoniporide, dexamethasone, aminoguanidine, and acetylsalicylic acid. Materials and Methods: Pharmacological properties were assessed using pH-dependent platelets deformation assay, anti-inflammatory activity assay on LPS-stimulated peritoneal macrophages, antiglycation assay, analysis of platelet aggregation in vitro and measurement of intraocular pressure in vivo. Results: Several compounds combine NHE-1 inhibition with antiglaucomic and antiplatelet activity. Compound 11 significantly inhibits pro-inflammatory activation of murine macrophages (IC50 15.64 µM) and effectively suppresses the formation of glycated proteins (38.1±2.6% in C 1 mM). Conclusion: The investigated compounds represent a promising scaffold for development of agents for the treatment of cardiovascular pathologies, glaucoma, excessive inflammation, and late diabetic complications including retina diabetics and thrombosis. [ABSTRACT FROM AUTHOR]

Background: Preservation of organ function and viability is a crucial factor for survival in cardiogenic shock (CS) patients. There is not information enough on cytoprotective substances that may delay organs damage in CS. We hypothesize that cytidine-5-diphosphocholine (CDP-choline) can act as a cytoprotective pharmacological measure that diminishes the target organ damage. So, we aimed to perform a review of works carried out in our institution to evaluate the effect of therapeutic cytoprotection of the CDP-choline. Summary: CDP-choline is an intermediate metabolite in the synthesis of phosphatidylcholine. It is also a useful drug for the treatment of acute ischaemic stroke, traumatic brain injury, and neurodegenerative diseases and has shown an excellent pharmacological safety profile as well. We review our institution's work and described the cytoprotective effects of CDP-choline in experimental models of heart, liver, and kidney acute damage, where this compound was shown to diminish reperfusion-induced ventricular arrhythmias, oxidative stress, apoptotic cell death, inflammation, lactic acid levels and to preserve mitochondrial function. Key Messages: We propose that additional research is needed to evaluate the impact of cytoprotective therapy adjuvant to mitigate target organ damage in patients with CS. [ABSTRACT FROM AUTHOR]

Magnoliae Flos (MF) is a medicinal herb widely employed in traditional medicine for relieving sinusitis, allergic rhinitis, headaches, and toothaches. Here, we investigated the potential preventive effects of MF extract (MFE) against 4-vinylcyclohexene diepoxide (VCD)-induced ovotoxicity in ovarian cells and a mouse model of premature ovarian insufficiency (POI). The cytoprotective effects of MFE were assessed using CHO-K1 or COV434 cells. In vivo, B6C3F1 female mice were intraperitoneally injected with VCD for two weeks to induce POI, while MFE was orally administered for four weeks, beginning one week before VCD administration. VCD led to a significant decline in the viabilities of CHO-K1 and COV434 cells and triggered excessive reactive oxygen species (ROS) production and apoptosis specifically in CHO-K1 cells. However, pretreatment with MFE effectively prevented VCD-induced cell death and ROS generation, while also activating the Akt signaling pathway. In vivo, MFE increased relative ovary weights, follicle numbers, and serum estradiol and anti-Müllerian hormone levels versus controls under conditions of ovary failure. Collectively, our results demonstrate that MFE has a preventive effect on VCD-induced ovotoxicity through Akt activation. These results suggest that MFE may have the potential to prevent and manage conditions such as POI and diminished ovarian reserve. [ABSTRACT FROM AUTHOR]

The silencing regulatory factor 2-like protein 3 (SIRT3) is a nicotinamide adenine dinucleotide (NAD+) dependent deacetylase located primarily in the mitochondria. This protein plays an important role in oxidative stress, energy metabolism, and autophagy in multicellular organisms. Autophagy (macroautophagy) is primarily a cytoprotective mechanism necessary for intracellular homeostasis and the synthesis, degradation, and recycling of cellular products. Autophagy can influence the progression of several neural, cardiac, hepatic, and renal diseases and can also contribute to the development of fibrosis, diabetes, and many types of cancer. Recent studies have shown that SIRT3 has an important role in regulating autophagy. Therefore in this study, we aimed to perform a literature review to summarize the role of SIRT3 in the regulation of cellular autophagy. The findings of this study could be used to identify new drug targets for SIRT3-related diseases. Methods: A comprehensive literature review of the mechanism involved behind SIRT3 and autophagy-related diseases was performed. Relevant literature published in Pubmed and Web of Science up to July 2023 was identified using the keywords "silencing regulatory factor 2-like protein 3", "SIRT3" and "autophagy". [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction Diabetes mellitus is a chronic metabolic disease that affects a large fraction of the world’s population. In addition to the many complications associated with it, the lack of effectiveness and insufficiency of current treatments have driven the WHO to return to traditional medicine, which generally involves the use of plant materials as remedies. Purpose This study investigates the protective effects of Dioscorea alata and D. rotundata extracts on the liver, pancreas, and kidney in alloxan-induced diabetic guinea pigs. Methods Diabetes was induced by a single intraperitoneal injection of alloxan (150 mg/kg). Post-induction, guinea pigs (Cavia porcellus L.) were treated orally with Dioscorea alata and D. rotundata extracts (200 mg/kg and 400 mg/kg, respectively) for 21 days. The liver, pancreas, and kidneys were assessed for histopathological changes. Two standard synthetic antidiabetics (insulin 5 IU/100g and glibenclamide 5 mg/kg) were used as positive controls. Results Histopathological examination revealed marked improvement in the tissue morphology of the liver, pancreas, and kidneys in the treated groups compared to the untreated group. The renal parenchyma showed a fairly normal structure, with the Malpighian glomerulus clearly visible, exhibiting hyperplastic cell nuclei in full regeneration. Conclusion Tuber extracts from these two yam species have shown potential to repair and regenerate tissue damaged by the deleterious effects of alloxan-induced free radicals and permanent hyperglycemia during diabetes. The evident antidiabetic and cytoprotective potential of these plant species could be utilized for the development of biologically active natural molecules for the treatment of diabetes mellitus and its complications. The study is limited by its short duration, and further long-term studies with varied dosage regimens are recommended to better understand the effects of these extracts. Additional research should explore the specific bioactive compounds responsible for the observed protective effects and their mechanisms of action.

Neurodegenerative disorders are difficult to treat because of natural barrier in the brain. Moreover, neurovascular units seem to be essential targets/mediators of the nervous system cytoprotective effects. Functionalized nanomaterials have gained significant prominence in the medical domain due to their extensive utilization in targeted drug delivery and therapeutics within the neurovascular system. Their remarkable potential in neurovascular therapy has been demonstrated, highlighting their effectiveness in this field. A systematic summary of the specific applications and limitations of functionalized nanomaterials in the targeted delivery system is essential for developing smart therapies to overcome the gaps in neurovascular therapy for the treatment of neurological disorders. The objective of present article was to highlight the advancements in recent therapies support the potential role of functionalized nanomaterials to tackle the difficulties in targeted delivery systems for neurodegenerative disorders. We review the role of functionalized nanomaterials as therapeutics within the neurovascular units and their potential to lead to more sophisticated and smart treatment techniques despite some obstacles, given to the patients of neurological disorders, particularly when paired with multimodal drugs who are likely to benefit from cytoprotection. This review also addresses the current understanding, gaps, and issues to be resolved.

Cisplatin is a prominent chemotherapeutic agent that can induce significant damage to normal cells. Therefore, it is important to develop agents that protect normal cells without influencing the chemotherapeutic effect of cisplatin. The present study was conducted to explore the protective effects of Annona muricata leaf polysaccharides (ALPS) against cisplatin‑induced toxicity in macrophages. Apoptosis was assessed in macrophages and lung cancer cells to investigate the cytoprotective effect of ALPS, their effect on the production of cisplatin‑induced reactive oxygen species (ROS) and the loss of the mitochondrial transmembrane potential (MTP). Cisplatin, when used alone or in combination with ALPS, showed significant toxicity against A549 and H460 lung cancer cells. However, cisplatin‑induced cytotoxicity was suppressed by cotreatment of RAW 264.7 macrophages with ALPS. ALPS significantly inhibited the upregulation of Bax, cytosolic cytochrome c and caspases‑3, ‑8 and ‑9. Moreover, ALPS resulted in the cleavage of PARP and downregulation of Bcl‑2 levels in a concentration‑dependent manner, which ultimately led to a reduction in the apoptotic and necrotic populations of cisplatin‑treated RAW 264.7 macrophages. The suppression of the apoptotic signaling pathways was mediated through the reduction of ROS and MTP loss in cisplatin‑treated RAW 264.7 macrophages. In addition, ALPS alleviated cell damage by suppressing the mitochondrial apoptotic pathways in cisplatin‑treated bone marrow‑derived macrophages. Together, these findings suggested that ALPS may alleviate the toxic side effects of chemotherapeutic agents and act as a potential candidate for use as an effective adjuvant therapy.

Introduction: Dysfunction of the endothelium impairs its' protective role and promotes inflammation and progression of vascular diseases. Activated Protein C (APC) elicits endothelial cytoprotective responses including barrier stabilization, anti-inflammatory and anti-apoptotic responses through the activation of the G protein-coupled receptor (GPCR) protease-activated receptor-1 (PAR1) and is a promising therapeutic. Despite recent advancements in developing new Activated protein C variants with clinical potential, the mechanism by which APC/PAR1 promotes different cytoprotective responses remains unclear and is important to understand to advance Activated protein C and new targets as future therapeutics. Here we examined the mechanisms by which APC/PAR1 attenuates cytokine-induced pro-inflammatory vascular cell adhesion molecule (VCAM-1) expression, a key mediator of endothelial inflammatory responses. Methods: Quantitative multiplexed mass spectrometry analysis of Activated protein C treated endothelial cells, endothelial cell transcriptomics database (EndoDB) online repository queries, biochemical measurements of protein expression, quantitative real-time polymerase chain reaction (RT-qPCR) measurement of mRNA transcript abundance, pharmacological inhibitors and siRNA transfections of human cultured endothelial cells. Results: Here we report that Activated Protein C modulates phosphorylation of tumor necrosis factor (TNF)-α signaling pathway components and attenuates of TNF-α induced VCAM-1 expression independent of mRNA stability. Unexpectedly, we found a critical role for the G protein-coupled receptor co-receptor sphingosine-1 phosphate receptor-1 (S1PR1) and the G protein receptor kinase-2 (GRK2) in mediating APC/PAR1 anti-inflammatory responses in endothelial cells. Discussion: This study provides new knowledge of the mechanisms by which different APC/PAR1 cytoprotective responses are mediated through discrete β-arrestin-2-driven signaling pathways modulated by specific G protein-coupled receptor co-receptors and GRKs.

Abstract Background Chemotherapy-induced alopecia (CIA) is a distressing adverse effect of chemotherapy, with an estimated incidence of 65% and limited treatment options. Cyclophosphamide (CYP) is a common alopecia-inducing chemotherapy agent. Human dental pulp stem cells (DPSCs) secrete several paracrine factors that up-regulate hair growth. Conditioned medium (CM) collected from DPSCs (DPSC-CM) promotes hair growth; culturing mesenchymal stem cells under hypoxic conditions can enhance this effect. Methods The effect of DPSC-CM cultured under normoxic (N-) and hypoxic (H-) conditions against CYP-mediated cytotoxicity in keratinocytes was examined using cell viability assay, lactate dehydrogenase (LDH) cytotoxicity assay, and apoptosis detection. The damage-response pathway was determined in a well-established CIA mouse model by analyzing macroscopic effects, histology, and apoptosis. Reverse transcription-quantitative PCR and Caspase-3/7 activity assay were used to investigate the impact of DPSC-CM on the molecular damage-response pathways in CYP-treated mice. The effect of post-CIA DPSC-CM application on post-CIA hair regrowth was analyzed by macroscopic effects and microstructure observation of the hair surface. Furthermore, to investigate the safety of DPSC-CM as a viable treatment option, the effect of DPSC-CM on carcinoma cell lines was examined by cell viability assay and a subcutaneous tumor model. Results In the cell viability assay, DPSC-CM was observed to increase the number of keratinocytes over varying CYP concentrations. Furthermore, it reduced the LDH activity level and suppressed apoptosis in CYP-treated keratinocytes. DPSC-CM exhibited the cytoprotective role in vivo via the dystrophic anagen damage-response pathway. While both N-CM and H-CM downregulated the Caspase-3/7 activity level, H-CM downregulated Caspase-3 mRNA expression. The proportion of post-CIA H-CM-treated mice with > 90% normal hair was nearly twice that of vehicle- or N-CM-treated mice between days 50 and 59 post-depilation, suggesting that post-CIA H-CM application may accelerate hair regrowth and improve hair quality. Furthermore, DPSC-CM suppressed proliferation in vitro in certain carcinoma cell lines and did not promote the squamous cell carcinoma (SCC-VII) tumor growth rate in mice. Conclusions The potentiality of DPSC-CM and H-CM as a promising cytoprotective agent and hair regrowth stimulant, respectively, for CIA needs in-depth exploration.

Background: (-)-Fenchone is a bicyclic monoterpene present in the plant species Foeniculum vulgare Mill, Thuja occidentalis L. (tuja), and Lavandula stoechas (lavender). These plants have therapeutic value in the treatment of intestinal disorders. Aim: To evaluate intestinal anti-inflammatory activity in an acute and chronic trinitrobenzene sulphonic acid (TNBS)-induced colitis model in rats. Methods: Intestinal anti-inflammatory effects were assessed using the acute and chronic TNBS-induced colitis model in rats. The mechanisms were evaluated from colonic tissue fragments of the acute and chronic models. Results: Oral administration of the (-)-fenchone (37.5–300 mg/kg) acute phase or (150 mg/kg) (p < 0.001) chronic phase reduced the macroscopic lesion score, ulcerative area, intestinal weight/length ratio, and diarrheal index in TNBS-treated animals. At a dose of 150 mg/kg, the acute and chronic phase decreased malondialdehyde (MDA) and myeloperoxidase (MPO) (p < 0.001), restored glutathione (GSH) levels and superoxide dismutase (SOD) (p < 0.001), decreased immunomarking for factor nuclear kappa B (NF-κB) and levels of interleukin (IL)-1 and tumor necrosis factor α (TNF-α), and maintained IL-10 and TGF-β basal levels. Furthermore, increased immunostaining for zonula occludens 1 (ZO-1) was observed. Conclusions: (-)-fenchone has intestinal anti-inflammatory activity related to cytoprotection of the intestinal barrier, as well as antioxidant and immunomodulatory effects.

There is a worrying scarcity of drug options for patients with severe COVID-19. Glycine possesses anti-inflammatory, cytoprotective, endothelium-protective, and platelet-antiaggregant properties, so its use in these patients seems promising. In this open label, controlled clinical trial, inpatients with severe COVID-19 requiring mechanical ventilation randomly received usual care (control group) or usual care plus 0.5 g/kg/day glycine by the enteral route (experimental group). Major outcomes included mortality, time to weaning from mechanical ventilation, total time on mechanical ventilation, and time from study recruitment to death. Secondary outcomes included laboratory tests and serum cytokines. Patients from experimental (n = 33) and control groups (n = 23) did not differ in basal characteristics. There were no differences in mortality (glycine group, 63.6% vs control group, 52.2%, p = 0.60) nor in any other major outcome. Glycine intake was associated with lower fibrinogen levels, either evaluated per week of follow-up (p < 0.05 at weeks 1, 2, and 4) or as weighted mean during the whole hospitalization (608.7 ± 17.7 mg/dl vs control 712.2 ± 25.0 mg/dl, p = 0.001), but did not modify any other laboratory test or cytokine concentration. In summary, in severe COVID-19 glycine was unable to modify major clinical outcomes, serum cytokines or most laboratory tests, but was associated with lower serum fibrinogen concentration. Registration: ClinicalTrials.gov NCT04443673, 23/06/2020. [ABSTRACT FROM AUTHOR]

Background: Cellular stress caused by noise-induced hearing loss can be observed through the damage of cochlear hair cells, mechanically and metabolically. SNR value on the DPOAE examination assesses the sensory function of cochlear outer hair cells. HSP70 as marker of cellular stress can be identified from its levels in blood and its expression in the cochlea. Methods: Three groups of rats were used for the noise intervention: Group 1 was the control group, Group 2 had a noise exposure of 100 dB, and Group 3 received a noise exposure of 110 dB. DPOAE examination was then conducted, blood samples from rats' tail were collected after a noise treatment, followed by the measurement of HSP70 levels by ELISA readings. Rats were terminated afterwards and immunohistochemical examination of the cochlear organ of Corti was performed to calculate the expression of HSP70. The data obtained were analyzed using SPSS. Results: A decrease occurred in the values of SNR and an increase occurred in HSP70 levels in blood along with its expression in the cochlea of noise model Rattus norvegicus, and there is a correlation between the three. Conclusion: The decrease in SNR values, increase in HSP70 levels in blood, and increase in HSP70 expression in the cochlear organ of Corti of Rattus norvegicus, proves that noise-induced hearing loss triggers the production of HSP70 as a cytoprotective agent in preventing inner ear damage. [ABSTRACT FROM AUTHOR]

Oxidovanadium(V) complexes, [(+)VOL1-5] and [(–)VOL1-5], with chiral tetradentate Schiff bases, which are products of monocondensation of S(‒)-3-amino-1,2-propanediol or R(+)-3-amino-1,2-propanediol with salicylaldehyde derivatives, have been synthesized. Different spectroscopic methods, viz. 1H and 51V NMR, IR, UV-Vis, and circular dichroism, as well as elemental analysis, have been used for their detailed characterization. Furthermore, the epoxidation of styrene, cyclohexene, and two monoterpenes, S(‒)-limonene and (‒)-α-pinene, using two oxidants, aqueous 30% H2O2 or tert-butyl hydroperoxide (TBHP) in decane, has been studied with catalytic amounts of all complexes. Finally, biological cytotoxicity studies have also been performed with these oxidovanadium(V) compounds for comparison with cis-dioxidomolybdenum(VI) Schiff base complexes with the same chiral ligands, as well as to determine the cytoprotection against the oxidative damage caused by 30% H2O2 in the HT-22 hippocampal neuronal cells in the range of their 10–100 μM concentration. [ABSTRACT FROM AUTHOR]

Though crucial for natural bone healing, local calcium ion (Ca2+) and phosphate ion (Pi) concentrations can exceed the cytotoxic limit leading to mitochondrial overload, oxidative stress, and cell death. For bone tissue engineering applications, H2S can be employed as a cytoprotective molecule to enhance mesenchymal stem cell (MSC) tolerance to cytotoxic Ca2+/Pi concentrations. Varied concentrations of sodium hydrogen sulfide (NaSH), a fast-releasing H2S donor, were applied to assess the influence of H2S on MSC proliferation. The results suggested a toxicity limit of 4 mM for NaSH and that 1 mM of NaSH could improve cell proliferation and differentiation in the presence of cytotoxic levels of Ca2+ (32 mM) and/or Pi (16 mM). To controllably deliver H2S over time, a novel donor molecule (thioglutamic acid—GluSH) was synthesized and evaluated for its H2S release profile. Excitingly, GluSH successfully maintained cytoprotective level of H2S over 7 days. Furthermore, MSCs exposed to cytotoxic Ca2+/Pi concentrations in the presence of GluSH were able to thrive and differentiate into osteoblasts. These findings suggest that the incorporation of a sustained H2S donor such as GluSH into CaP-based bone graft substitutes can facilitate considerable cytoprotection, making it an attractive option for complex bone regenerative engineering applications. [ABSTRACT FROM AUTHOR]

Nowadays, the unique features of nanoparticles (NPs) have encouraged new applications in different areas including biology, medicine, agriculture, and electronics. Their quick joining into daily life not only enhances the uses of NPs in a wide range of modern technologies but also their release into the aquatic environment causes inevitable environmental concerns. On the other hand boron exhibits key physiological effects on biological systems. This research was designed for evaluating the toxicity of magnetite nanoparticles (Fe3O4-MNPs) on aquatic organisms and obtaining data for the information gap in this area. In this study, Rainbow trout (Oncorhynchus mykiss) was considered as an aquatic indicator, and trials were designed as Ulexite (a boron mineral, UX) treatment against exposure to Fe3O4-MNPs. Synthesized and characterized Fe3O4-MNPs were exposed to rainbow trouts in wide spectrum concentrations (0.005–0.08 mL/L) to analyze its lethal dose (LC50) and cytoprotective properties by UX treatment were assessed against Fe3O4-MNPs applications for 96 h. For the initial toxicity analysis, hematological parameters (blood cell counts) were examined in experimental groups and micronucleus (MN) assay was performed to monitor nuclear abnormalities after exposure to NPs. Biochemical analyzes in both blood and liver samples were utilized to assess antioxidant/oxidative stress and inflammatory parameters. Also, 8-hydroxy-2'-deoxyguanosine (8-OHdG) assay was used to investigate oxidative DNA lesions and Caspase-3 analysis was performed on both blood and liver tissues to monitor apoptotic cell death occurrence. When antioxidant enzymes in blood and liver tissue were examined, time-dependent decreases in activity were determined in SOD, CAT, GPx, and GSH enzymes, while increased levels of MDA and MPO parameters were observed in respect to Fe3O4-MNPs exposure. It was found that TNF-α, Il-6 levels were enhanced against Fe3O4-MNPs treatment, but Nrf-2 levels were decreased at the 46th and 96th h. In the 96th application results, all parameters were statistically significant (p < 0.05) in blood and liver tissue, except for the IL-6 results. It was determined that the frequency of MN, the level of 8-OHdG and caspase-3 activity increased in respect to Fe3O4-MNPs exposure over time. Treatment with UX alleviated Fe3O4-MNPs-induced hematotoxic and hepatotoxic alterations as well as oxidative and genetic damages. Our findings offer strong evidence for the use of UX as promising, safe and natural protective agents against environmental toxicity of magnetite nanoparticles. [ABSTRACT FROM AUTHOR]

Despite the significant progress in the fields of biology, physiology, molecular medicine, and pharmacology; the designation of the properties of nitrogen monoxide in the regulation of life-supporting functions of the organism; and numerous works devoted to this molecule, there are still many open questions in this field. It is widely accepted that nitric oxide (•NO) is a unique molecule that, despite its extremely simple structure, has a wide range of functions in the body, including the cardiovascular system, the central nervous system (CNS), reproduction, the endocrine system, respiration, digestion, etc. Here, we systematize the properties of •NO, contributing in conditions of physiological norms, as well as in various pathological processes, to the mechanisms of cytoprotection and cytodestruction. Current experimental and clinical studies are contradictory in describing the role of •NO in the pathogenesis of many diseases of the cardiovascular system and CNS. We describe the mechanisms of cytoprotective action of •NO associated with the regulation of the expression of antiapoptotic and chaperone proteins and the regulation of mitochondrial function. The most prominent mechanisms of cytodestruction—the initiation of nitrosative and oxidative stresses, the production of reactive oxygen and nitrogen species, and participation in apoptosis and mitosis. The role of •NO in the formation of endothelial and mitochondrial dysfunction is also considered. Moreover, we focus on the various ways of pharmacological modulation in the nitroxidergic system that allow for a decrease in the cytodestructive mechanisms of •NO and increase cytoprotective ones. [ABSTRACT FROM AUTHOR]

Copyright of Revista Biomedica is the property of Centro de Investigaciones Regionales Dr. Hideyo Noguchi; Facultad de Medicina, UADY and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)