C23 ameliorates carbon tetrachloride-induced liver fibrosis in mice.

BACKGROUND: C23, an oligo-peptide derived from cold-inducible RNA-binding protein (CIRP), has been reported to inhibit tissue inflammation, apoptosis and fibrosis by binding to the CIRP receptor; however, there are few reports on its role in liver fibrosis and the underlying mechanism is unknown. AIM: To explore whether C23 plays a significant role in carbon tetrachloride (CCl4)-induced liver fibrosis. METHODS: CCl4 was injected for 6 weeks to induce liver fibrosis and C23 was used beginning in the second week. Masson and Sirius red staining were used to examine changes in fiber levels. Inflammatory factors in the liver were detected and changes in α-smooth muscle actin (α-SMA) and collagen I expression were detected via immunohistochemical staining to evaluate the activation of hematopoietic stellate cells (HSCs). Western blotting was used to detect the activation status of the transforming growth factor-beta (TGF-ß)/Smad3 axis after C23 treatment. RESULTS: CCl4 successfully induced liver fibrosis in mice, while tumor necrosis factor-alpha (TNF-α), IL (interleukin)-1ß, and IL-6 levels increased significantly and the IL-10 level decreased significantly. Interestingly, C23 inhibited this process. On the other hand, C23 significantly inhibited the activation of HSCs induced by CCl4, which inhibited the expression of α-SMA and the synthesis of collagen I. In terms of mechanism, C23 can block Smad3 phosphorylation significantly and inhibits TGF-ß/Smad3 pathway activation, thereby improving liver injury caused by CCl4. CONCLUSION: C23 may block TGF-ß/Smad3 axis activation, inhibit the expression of inflammatory factors, and inhibit the activation of HSCs induced by CCl4, alleviating liver fibrosis.

Solid Lipid Nanoparticles Incorporated with Retinol and Pentapeptide-18-Optimization, Characterization, and Cosmetic Application.

Solid lipid nanoparticles (SLNs) incorporated with retinol and oligopeptide can have a full spectrum of effects on the skin as a compatible combination of ingredients with broad anti-aging properties. The research's main objective was to ensure the stability of lipid nanocarriers containing retinol and peptide due to the planned use of this dispersion as a cosmetic raw material. To confirm the effectiveness of method optimization (high shear homogenization, HSH) and proper selection of substrates, SLN dispersions were obtained in three combinations: 1-non-incorporated SLNs; 2-SLNs containing only retinol; 3-SLNs containing retinol and pentapeptide-18; these were then stored at different temperatures (4, 25, 45 °C) for 4 weeks. The desired values of the physicochemical parameters of the optimized dispersion of lipid nanoparticles incorporated with retinol and oligopeptide over the required storage period were confirmed: mean particle size (Z-Ave) = 134.7 ± 0.3 nm; polydispersity index (PDI) = 0.269 ± 0.017 [-]; zeta potential (ZP) = 42.7 ± 1.2 mV (after 4 weeks at 25 °C). The results confirmed the proper selection of the SLN production method and the effectiveness of the optimization performed. The possibility of using the obtained raw material as an ingredient in cosmetic products with anti-aging properties was indicated.

DNA/RNA heteroduplex technology with cationic oligopeptide reduces class-related adverse effects of nucleic acid drugs.

Antisense oligonucleotides (ASOs) are a therapeutic modality for incurable diseases. However, systemic injection of gapmer-type ASOs causes class-related toxicities, including prolongation of activated partial thromboplastin time (aPTT) and thrombocytopenia. We previously reported that cholesterol-conjugated DNA/RNA heteroduplex oligonucleotides (Chol-HDOs) exhibit significantly enhanced gene-silencing effects compared to ASOs, even in the central nervous system, by crossing the blood-brain barrier. In the present study, we initially evaluated the effect of the HDO structure on class-related toxicities. The HDO structure ameliorated the class-related toxicities associated with ASOs, but they remained to some extent. As a further antidote, we have developed artificial cationic oligopeptides, L-2,4-diaminobutanoic acid oligomers (DabOs), which bind to the phosphates in the major groove of the A-type double-helical structure of HDOs. The DabO/Chol-HDO complex showed significantly improved aPTT prolongation and thrombocytopenia in mice while maintaining gene-silencing efficacy. Moreover, the conjugation with DabOs effectively prevented cerebral infarction, a condition frequently observed in mice intravenously injected with high-dose Chol-HDO. These approaches, combining HDO technology with DabOs, offer distinct advantages over conventional strategies in reducing toxicities. Consequently, the DabO/HDO complex represents a promising platform for overcoming the class-related toxicities associated with therapeutic ASOs.

Bioconversion of agriculture by-products with functionally enhanced Streptomyces sp. SCUT-3: Fish skin as a model.

With the global population continuously rising, efficient bioconversion of inedible agricultural by-products is crucial for human food and energy sustainability. We here propose solid-state fermentation approaches to efficiently convert biopolymers into oligomers/monomers by accelerating the natural degradation process of the versatile Streptomyces sp. strain SCUT-3. Using fish skin as a representative by-product, 54.3 g amino acids and 14.7 g peptides (91 % < 2500 Da) were recovered from 89.0 g protein in 100 g tilapia skin sample by collagenase-overexpressed SCUT-3 for seven days at a 1:4 substrate:liquid ratio. Fish skin collagen hydrolysates exhibited excellent anti-oxidation, anti-hypertension, scratch-repairing, anti-aging, anti-ultraviolet radiation, and anti-inflammation effects on human skin fibroblasts In vitro and zebrafish larvae in vivo, indicating their potential applications in healthcare/skincare and anti-atopic dermatitis. As Laozi said, the divine law follows nature. This study underscores the efficacy of genetically engineered SCUT-3 according to its natural biomass utilization laws in large-scale biopolymer conversion.

Anaerobic degradation of excess protein-rich fish feed drives CH4 ebullition in a freshwater aquaculture pond.

Aquaculture is a climate-relevant source of greenhouse gases like methane. Methane emissions depend on various parameters, with organic matter playing a crucial role. Nevertheless, little is known about the composition of organic matter in aquaculture. We investigated the effects of excessive loading of high-protein fish feed on the quality of sediment organic matter in a fishpond to explain extremely high methane ebullition rates (bubble flux). Analysing the molecular composition of water-extractable organic matter using liquid chromatography Fourier-transform ion cyclotron resonance mass spectroscopy, we found strong differences between the feeding area and open water area: low-molecular weight nitrogen and sulphur-rich organic compounds were highly enriched at the feeding area. In addition, methane ebullition correlated well with sediment protein content and total bound nitrogen in pore water. Our results indicate that feed proteins in the sediments are hydrolysed into oligopeptides (CHNO) and subsequently converted to CHOS and CHNOS components during anaerobic deamination of protein and peptide fragments in the presence of inorganic sulphides. These metabolites accumulate at the feeding area due to continuous feed supply. Our findings illustrate the adverse effects of excessive feeding leading to bioreactor-like methane emissions at the feeding area. Improving feed management has the potential to make aquaculture more climate-friendly.

Metabolic reprogramming of corn oligopeptide in regulating sodium nitrite-induced canine hepatocyte injury via TGF/NF-κB signaling pathways and aminoacyl-tRNA biosynthesis.

Sodium nitrite (SN), a prevalent food preservative, is known to precipitate hepatotoxicity upon exposure. This study elucidates the hepatoprotective effects of corn oligopeptide (COP) and vitamin E (VE) against SN-induced hepatic injury in canine hepatocytes. Canine liver cells were subjected to SN to induce hepatotoxicity, followed by treatment with COP and VE. Evaluations included assays for cell viability, oxidative stress markers, apoptosis, and inflammatory cytokines. Additionally, transcriptomic and metabolomic analyses were performed to delineate the underlying molecular mechanisms. The findings demonstrated that COP and VE significantly ameliorated SN-induced cytotoxicity, oxidative stress, and apoptosis. It was evidenced by restored cell viability, enhanced antioxidant enzyme activity, reduced cytoplasmic enzyme leakage, and decreased levels of malondialdehyde and inflammatory cytokines, with COP showing superior efficacy. The RNA sequencing revealed that COP treatment suppressed the SN-activated aminoacyl-tRNA biosynthesis pathway and TGF-ß/NF-κB signaling pathways, thereby mitigating amino acid depletion, apoptosis, and inflammation. Moreover, COP treatment upregulated genes associated with protein folding, bile acid synthesis, and DNA repair. Metabolomic analysis corroborated these results, showing that COP restored amino acid levels and enhanced bile acid metabolism, alleviating SN-induced metabolic disruptions. These findings offered significant insights into the protective mechanisms of COP underscoring its prospective application in treating liver injuries.

Phloem-specific overexpression of AtOPT6 alters glutathione, phytochelatin, and cadmium distribution in Arabidopsis thaliana.

The Arabidopsis oligopeptide transporter AtOPT6 is reportedly involved in the long-distance transport of thiol compounds into sink organs. In the present study, transgenic Arabidopsis lines overexpressing AtOPT6 under the control of a phloem-specific promoter, sucrose-proton symporter 2 (pSUC2), were analyzed for thiol and cadmium (Cd) distribution during the reproductive stage, both with and without Cd exposure. Phloem specific AtOPT6-overexpressing lines did not exhibit an evident impact on bolting time. In the absence of Cd exposure, these transgenic lines showed significantly enhanced transport of endogenous glutathione into siliques, accompanied by a reduction in the glutathione content of flowers and roots during the reproductive stage. Additionally, exposure of the roots of the phloem specific AtOPT6-overexpressing lines to Cd altered the distribution of thiol compounds, resulting in an increase in the content of phytochelatins in sink organs, contributing to a significant elevation of Cd contents in reproductive sink. Our findings confirm the crucial role of AtOPT6 in unloading phytochelatin-Cd conjugates from the phloem into sink organ.

[Place of oligopeptide H-Met-Glu-His-Phe-Pro-Gly-Pro-OH in the therapy and rehabilitation of patients with ischemic stroke]. / Mesto oligopeptida H-Met-Glu-His-Phe-Pro-Gly-Pro-OH v terapii i reabilitatsii patsientov s ishemicheskim insul'tom.

Cerebrovascular diseases (CVDs) are one of the leading causes of death and disability In Russia: they rank second in the structure of mortality from diseases of the circulatory system and in the overall mortality of the population. Successful treatment of CVD involves an integrated approach to the problem, taking into account the compensation of cardiovascular disorders, the elimination of neurological and psychopathological syndromes, the improvement of cerebral circulation and the use of neuroprotective agents that increase the resistance of brain tissue to hypoxia and ischemia. Insufficient clinical efficacy of neuroprotectors is due to a number of objective reasons, of which only two are universal. The first of these reasons is the timing of the start of therapy in the clinic, as a rule, is outside the «therapeutic window¼; the second reason is the fact that disturbance of the patency of the cerebral vessels in the affected area makes it difficult or impossible to deliver the drug to the penumbra area. The way out of this situation is the intranasal route of drug administration, which is characteristic for the analogs of regulatory peptides such as for H-Met-Glu-His-Phe-Pro-Gly-Pro-OH (MGHPPGP). The review of clinical studies indicates that MGHPPGP is clinically effective in the treatment of ischemic stroke both in the acute period of stroke and in the recovery period. The clinical efficacy of MGHPPGP was shown both in atherothrombotic and cardioembolic subtypes of stroke, against the background of blood flow disturbances in both the carotid and vertebrobasilar systems.

Bat-derived oligopeptide LE6 inhibits the contact-kinin pathway and harbors anti-thromboinflammation and stroke potential.

Thrombosis and inflammation are primary contributors to the onset and progression of ischemic stroke. The contact-kinin pathway, initiated by plasma kallikrein (PK) and activated factor XII (FXIIa), functions bidirectionally with the coagulation and inflammation cascades, providing a novel target for therapeutic drug development in ischemic stroke. In this study, we identified a bat-derived oligopeptide from Myotis myotis (Borkhausen, 1797), designated LE6 (Leu-Ser-Glu-Glu-Pro-Glu, 702 Da), with considerable potential in stroke therapy due to its effects on the contact kinin pathway. Notably, LE6 demonstrated significant inhibitory effects on PK and FXIIa, with inhibition constants of 43.97 µmol/L and 6.37 µmol/L, respectively. In vitro analyses revealed that LE6 prolonged plasma recalcification time and activated partial thromboplastin time. In murine models, LE6 effectively inhibited carrageenan-induced mouse tail thrombosis, FeCl 3-induced carotid artery thrombosis, and photochemically induced intracerebral thrombosis. Furthermore, LE6 significantly decreased inflammation and stroke injury in transient middle cerebral artery occlusion models. Notably, the low toxicity, hemolytic activity, and bleeding risk of LE6, along with its synthetic simplicity, underscore its clinical applicability. In conclusion, as an inhibitor of FXIIa and PK, LE6 offers potential therapeutic benefits in stroke treatment by mitigating inflammation and preventing thrombus formation.

Antimicrobial Activity of Positively Charged Oligopeptides with Theoretical High α-Helix Content against Cutibacterium acnes.

Cutibacterium acnes is abundant and commonly exists as a superficial bacteria on human skin. Recently, the resistance of C. acnes to antimicrobial agents has become a serious concern, necessitating the development of alternative pharmaceutical products with antimicrobial activity against C. acnes. To address this need, we evaluated the antimicrobial activity of CKR-13-a mutant oligopeptide of FK-13 with increased net charge and theoretical α-helical content-against C. acnes in modified Gifu Anaerobic Medium broth by determining the minimum inhibitory concentration (MIC). CKR-13 exerted greater antimicrobial activity against C. acnes than FK-13 in the broth at pH 7.0. The antimicrobial activity of CKR-13 with RXM against C. albicans was pH-dependent. The ionization of CKR-13 and pH-dependent growth delay of C. albicans was suggested to be associated with the increase in CKR-13 antimicrobial activity.

Identification and Free Radical Scavenging Activity of Oligopeptides from Mixed-Distillate Fermented Baijiu Grains and Soy Sauce Residue.

This study aimed to explore the potential antioxidant activity and mechanism of oligopeptides from sauce-aroma Baijiu. The oligopeptides of Val-Leu-Pro-Phe (VLPF), Pro-Leu-Phe (PLF), Val-Gly-Phe-Cys (VGFC), Leu-Tyr-Pro (LYP), Leu-Pro-Phe (LPF), and Phe-Thr-Phe (FTF) were identified by liquid chromatography-mass spectrometry (LC-MS) from the mixed-distillate of Baijiu fermented grains and soy sauce residue (MDFS). The antioxidant mechanism of these oligopeptides on scavenging DPPH•, ABTS•+, and hydroxide radicals was investigated, respectively. Among them, VGFC had the strongest potential antioxidant activity, which was responsible for its hydrogen bonds with these radicals with high affinity. The binding energies between VGFC and these radicals were -1.26 kcal/mol, -1.33 kcal/mol, and -1.93 kcal/mol, respectively. Additionally, free radicals prefer to bind the oligopeptide composed of hydrophobic amino acid residues such as Leu, Val, Phe, and Pro, thus being scavenged for exerting antioxidant activity. It provided a new idea for the development and utilization of bioactive oligopeptides in sauce-aroma Baijiu.

An oligo peptide transporter family member, OsOPT7, mediates xylem unloading of Fe for its preferential distribution in rice.

Iron (Fe) needs to be delivered to different organs and tissues of above-ground parts for playing its multiple physiological functions once it is taken up by the roots. However, the mechanisms underlying Fe distribution are poorly understood. We functionally characterized OsOPT7, a member of oligo peptide transporter family in terms of expression patterns, localization, transport activity and phenotypic analysis of knockdown lines. OsOPT7 was highly expressed in the nodes, especially in the uppermost node I, and its expression was upregulated by Fe-deficiency. OsOPT7 transports ferrous iron into the cells coupled with proton. Immunostaining revealed that OsOPT7 is mainly localized in the xylem parenchyma cells of the enlarged vascular bundles in the nodes and vascular tissues in the leaves. Knockdown of OsOPT7 did not affect the Fe uptake, but altered Fe distribution; less Fe was distributed to the new leaf, upper nodes and developing panicle, but more Fe was distributed to the old leaves. Furthermore, knockdown of OsOPT7 also resulted in less Fe distribution to the leaf sheath, but more Fe to the leaf blade. Taken together, OsOPT7 is involved in the xylem unloading of Fe for both long-distance distribution to the developing organs and local distribution within the leaf in rice.

Effects of Wheat Oligopeptide on the Baking and Retrogradation Properties of Bread Rolls: Evaluation of Crumb Hardness, Moisture Content, and Starch Crystallization.

Delaying the deterioration of bakery goods is necessary in the food industry. The objective of this study was to determine the effects of wheat oligopeptide (WOP) on the qualities of bread rolls. The effects of WOP on the baking properties, moisture content, and starch crystallization of rolls during the storage process were investigated in this study. The results showed that WOP effectively improved the degree of gluten cross-linking, thereby improving the specific volume and the internal structure of rolls. The FTIR and XRD results showed that the addition of WOP hindered the formation of the starch double helix structure and decreased its relative crystallinity. The DSC results revealed a decrease in the enthalpy change (ΔH) from 0.812 to 0.608 J/g after 7 days of storage with 1.0% WOP addition, further indicating that WOP reduced the availability of water for crystal lattice formation and hindered the rearrangement of starch molecules. The addition of WOP also improved the microstructure of the rolls that were observed using SEM analysis. In summary, WOP is expected to be an effective natural additive to inhibit starch staling and provide new insights into starchy food products.

Acetylated oligopeptide and N-acetylcysteine protect against iron overload-induced dentate gyrus hippocampal degeneration through upregulation of Nestin and Nrf2/HO-1 and downregulation of MMP-9/TIMP-1 and GFAP.

Iron accumulation in the brain causes oxidative stress, blood-brain barrier (BBB) breakdown, and neurodegeneration. We examined the preventive effects of acetylated oligopeptides (AOP) from whey protein on iron-induced hippocampal damage compared to N-acetyl cysteine (NAC). This 5-week study used 40 male albino rats. At the start, all rats received 150 mg/kg/day of oral NAC for a week. The 40 animals were then randomly divided into four groups: Group I (control) received a normal diet; Group II (iron overload) received 60 mg/kg/day intraperitoneal iron dextran 5 days a week for 4 weeks; Group III (NAC group) received 150 mg/kg/day NAC and iron dextran; and Group IV (AOP group) received 150 mg/kg/day AOP and iron dextran. Enzyme-linked immunosorbent assay, spectrophotometry, and qRT-PCR were used to measure MMP-9, tissue inhibitor metalloproteinase-1 (TIMP-1), MDA, reduced glutathione (GSH) levels, and nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) gene expression. Histopathological and immunohistochemical detection of nestin, claudin, caspase, and GFAP was also done. MMP-9, TIMP-1, MDA, caspase, and GFAP rose in the iron overload group, while GSH, Nrf2, HO-1, nestin, and claudin decreased. The NAC and AOP administrations improved iron overload-induced biochemical and histological alterations. We found that AOP and NAC can protect the brain hippocampus from iron overload, improve BBB disruption, and provide neuroprotection with mostly no significant difference from healthy controls.

Engineered exosomes with enhanced stability and delivery efficiency for glioblastoma therapy.

Due to the blood-brain barrier (BBB), the application of chemical drugs for glioblastoma treatment is severely limited. Recently, exosomes have been widely applied for drug delivery to the brain. However, the differences in brain targeting efficiency among exosomes derived from different cell sources, as well as the premature drug leakage during circulation, still limit the therapeutic efficacy. Here, we designed a functional oligopeptide-modified exosome loaded with doxorubicin (Pep2-Exos-DOX) for glioblastoma treatment. BV2 mouse microglial cell line was selected as the exosome source due to the favorable BBB penetration. To avoid drug release in the circulation, a redox-response oligopeptide was designed for incorporation into the membranes of exosomes to lock the drug during circulation. The enrichment of the drug in glioblastoma was confirmed. Pharmacodynamic evaluation showed Pep2-Exos-DOX possessed significant anti-cancer activity against glioblastoma as well as relative biosafety. This exosome-based drug delivery system modified with redox-response oligopeptides provides us a novel strategy for brain diseases treatment.

Activation of M1 muscarinic acetylcholine receptors by proline-rich oligopeptide 7a (Bothrops jararaca snake venom rescues oxidative stress-induced neurotoxicity in PC12 cells.

Background: The bioactive peptides derived from snake venoms of the Viperidae family species have been promising as therapeutic candidates for neuroprotection due to their ability to prevent neuronal cell loss, injury, and death. Therefore, this study aimed to evaluate the cytoprotective effects of a synthetic proline-rich oligopeptide 7a (PRO-7a;

Potential nutritional strategies to prevent and reverse sarcopenia in aging process: Role of fish oil-derived ω-3 polyunsaturated fatty acids, wheat oligopeptide and their combined intervention.

INTRODUCTION: Nutritional support is potentially considered an essential step to prevent muscle loss and enhance physical function in older adults. OBJECTIVES: This study aimed to assess the role of potential nutritional strategies, i.e., fish oil-derived ω-3 polyunsaturated fatty acids (PUFAs), wheat oligopeptide and their combined intervention, in preventing and reversing sarcopenia in aging process. METHODS: One hundred 25-month-old Sprague-Dawley rats were randomly divided into 10 groups, and 10 newly purchased 6-month-old rats were included in young control group (n = 10). Fish oil (200, 400 or 800 mg/kg body weight), wheat oligopeptide (100, 200 or 400 mg/kg body weight), fish oil + wheat oligopeptide (800 + 100, 400 + 200 or 200 + 400 mg/kg body weight) or the equal volume of solvent were administered daily by gavage for 10 weeks. The effects of these interventions on natural aging rats were evaluated. RESULTS: All intervention groups had a significant increase in muscle mass and grip strength and reduction in perirenal fat weight when compared to the aged control group (P < 0.05). The results of biochemical parameters, magnetic resonance imaging, proteomics and western blot suggested that the combination of wheat oligopeptide and fish oil-derived ω-3 PUFA, especially group WFM 2 (400 + 200 mg/kg body weight fish oil + wheat oligopeptide), was found to be more effective against aging-associated muscle loss than single intervention. Additionally, the interventions ameliorated fatty infiltration, muscle atrophy, and congestion in the intercellular matrix, and inflammatory cell infiltration in muscle tissue. The interventions also improved oxidative stress, anabolism, hormone levels, and inflammatory levels of skeletal muscle. CONCLUSIONS: The combination of fish oil-derived ω-3 PUFA and wheat oligopeptide was found to be a promising nutritional support to prevent and reverse sarcopenia. The potential mechanism involved the promotion of protein synthesis and muscle regeneration, as well as the enhancement of muscle strength.

Enforcing Local DNA Kinks by Sequence-Selective Trisintercalating Oligopeptides of a Tricationic Porphyrin: A Polarizable Molecular Dynamics Study.

Bisacridinyl-bisarginyl porphyrin (BABAP) is a trisintercalating derivative of a tricationic porphyrin, formerly designed and synthesized in order to selectively target and photosensitize the ten-base pair palindromic sequence d(CGGGCGCCCG)2 . We resorted to the previously derived (Far et al., 2004) lowest energy-minimized (EM) structure of the BABAP complex with this sequence as a starting point. We performed polarizable molecular dynamics (MD) on this complex. It showed, over a 150 ns duration, the persistent binding of the Arg side-chain on each BABAP arm to the two G bases upstream from the central porphyrin intercalation site. We subsequently performed progressive shortenings of the connector chain linking the Arg-Gly backbone to the acridine, from n=6 methylenes to 4, followed by removal of the Gly backbone and further connector shortenings, from n=4 to n=1. These resulted into progressive deformations ('kinks') of the DNA backbone. In its most accented kinked structure, the DNA backbone was found to have a close overlap with that of DNA bound to Cre recombinase, with, at the level of one acridine intercalation site, negative roll and positive tilt values consistent with those experimentally found for this DNA at its own kinked dinucleotide sequence. Thus, in addition to their photosensitizing properties, some BABAP derivatives could induce sequence-selective, controlled DNA deformations, which are targets for cleavage by endonucleases or for repair enzymes.

Activation of M1 muscarinic acetylcholine receptors by proline-rich oligopeptide 7a (

Background: The bioactive peptides derived from snake venoms of the Viperidae family species have been promising as therapeutic candidates for neuroprotection due to their ability to prevent neuronal cell loss, injury, and death. Therefore, this study aimed to evaluate the cytoprotective effects of a synthetic proline-rich oligopeptide 7a (PRO-7a; <EDGPIPP) from Bothrops jararaca snake, on oxidative stress-induced toxicity in neuronal PC12 cells and astrocyte-like C6 cells. Methods: Both cells were pre-treated for four hours with different concentrations of PRO-7a, submitted to H2O2-induced damage for 20 h, and then the oxidative stress markers were analyzed. Also, two independent neuroprotective mechanisms were investigated: a) L-arginine metabolite generation via argininosuccinate synthetase (AsS) activity regulation to produce agmatine or polyamines with neuroprotective properties; b) M1 mAChR receptor subtype activation pathway to reduce oxidative stress and neuron injury. Results: PRO-7a was not cytoprotective in C6 cells, but potentiated the H2O2-induced damage to cell integrity at a concentration lower than 0.38 μM. However, PRO-7a at 1.56 µM, on the other hand, modified H2O2-induced toxicity in PC12 cells by restoring cell integrity, mitochondrial metabolism, ROS generation, and arginase indirect activity. The α-Methyl-DL-aspartic acid (MDLA) and L-NΩ-Nitroarginine methyl ester (L-Name), specific inhibitors of AsS and nitric oxide synthase (NOS), which catalyzes the synthesis of polyamines and NO from L-arginine, did not suppress PRO-7a-mediated cytoprotection against oxidative stress. It suggested that its mechanism is independent of the production of L-arginine metabolites with neuroprotective properties by increased AsS activity. On the other hand, the neuroprotective effect of PRO-7a was blocked in the presence of dicyclomine hydrochloride (DCH), an M1 mAChR antagonist. Conclusions: For the first time, this work provides evidence that PRO-7a-induced neuroprotection seems to be mediated through M1 mAChR activation in PC12 cells, which reduces oxidative stress independently of AsS activity and L-arginine bioavailability.(AU)

Confinement of Oligopeptides by Terminally Functionalized Polyisoprene to Improve Their Mechanical Strength, Creep Resistance, and Antifatigue Properties.

A small amount of terminal polar phase endows natural rubber (NR) with excellent comprehensive properties superior to those of synthetic isoprene rubber. In this work, the comprehensive properties of synthetic rubber were remarkably improved by introducing a stable terminal nanoconfinement structure by combining terminal hydroxyl groups and pentapeptide molecules noncovalently into the same phases. The results show that the stable terminal phases hardly affect the free chain motion but enhance the entanglement. Under cyclic loading, the terminal polar phases undergo hierarchically structural changes such as reversible dissociation of the weak bonds, phase deformation, and crystalline reorganization, all of which dissipate the stress and are beneficial for high strength and extensibility. At the same time, synthetic rubbers demonstrate much superior fatigue resistance and lower hysteresis relative to NR and maintain comparable dimensional stability. This strategy suggests that the comprehensive properties of elastomers can be regulated and upgraded by facile terminal noncovalent interactions.