In silico and in vivo discovery of antioxidant sea cucumber peptides with antineurodegenerative properties.

Since oxidative stress is often associated with neurodegenerative diseases, antioxidants are likely to confer protection against neurodegeneration. Despite an increasing number of food-derived peptides being identified as antioxidants, their antineurodegenerative potentials remain largely unexplored. Here, a sea cucumber peptide preparation - the peptide-rich fraction of <3 kDa (UF<3K) obtained by ultrafiltration from Apostichopus japonicus protein hydrolyzate - was found to protect PC12 cells and Caenorhabditis elegans from neurodegeneration by reducing oxidative stress and apoptosis, demonstrating its in vitro and in vivo neuroprotective effects. As many food-originated peptides are cryptides (cryptic peptides - short amino acid sequences encrypted in parent proteins) released in quantities by protein hydrolysis, UF<3K was subjected to sequencing analysis. As expected, a large repertoire of peptides were identified in UF<3K, establishing a sea cucumber cryptome (1238 peptides in total). Then 134 peptides were randomly selected from the cryptome (>10%) and analyzed for their antioxidant activities using a number of in silico bioinformatic programs as well as in vivo experimental assays in C. elegans. From these results, a novel antioxidant peptide - HoloPep#362 (FETLMPLWGNK) - was shown to not only inhibit aggregation of neurodegeneration-associated polygluatmine proteins but also ameliorate behavioral deficits in proteotoxicity nematodes. Proteomic analysis revealed an increased expression of several lysosomal proteases by HoloPep#362, suggesting proteostasis maintenance as a mechanism for its antineurodegenerative action. These findings provide an insight into the health-promoting potential of sea cucumber peptides as neuroprotective nutraceuticals and also into the importance of training in silico peptide bioactivity prediction programs with in vivo experimental data.

Mulberry and Hippophae-based solid beverage promotes weight loss in rats by antagonizing white adipose tissue PPARγ and FGFR1 signaling.

Obesity, a multifactorial disease with many complications, has become a global epidemic. Weight management, including dietary supplementation, has been confirmed to provide relevant health benefits. However, experimental evidence and mechanistic elucidation of dietary supplements in this regard are limited. Here, the weight loss efficacy of MHP, a commercial solid beverage consisting of mulberry leaf aqueous extract and Hippophae protein peptides, was evaluated in a high-fat high-fructose (HFF) diet-induced rat model of obesity. Body component analysis and histopathologic examination confirmed that MHP was effective to facilitate weight loss and adiposity decrease. Pathway enrichment analysis with differential metabolites generated by serum metabolomic profiling suggests that PPAR signal pathway was significantly altered when the rats were challenged by HFF diet but it was rectified after MHP intervention. RNA-Seq based transcriptome data also indicates that MHP intervention rectified the alterations of white adipose tissue mRNA expressions in HFF-induced obese rats. Integrated omics reveals that the efficacy of MHP against obesogenic adipogenesis was potentially associated with its regulation of PPARγ and FGFR1 signaling pathway. Collectively, our findings suggest that MHP could improve obesity, providing an insight into the use of MHP in body weight management.

Abalone peptide increases stress resilience and cost-free longevity via SKN-1-governed transcriptional metabolic reprogramming in C. elegans.

A major goal of healthy aging is to prevent declining resilience and increasing frailty, which are associated with many chronic diseases and deterioration of stress response. Here, we propose a loss-or-gain survival model, represented by the ratio of cumulative stress span to life span, to quantify stress resilience at organismal level. As a proof of concept, this is demonstrated by reduced survival resilience in Caenorhabditis elegans exposed to exogenous oxidative stress induced by paraquat or with endogenous proteotoxic stress caused by polyglutamine or amyloid-ß aggregation. Based on this, we reveal that a hidden peptide ("cryptide")-AbaPep#07 (SETYELRK)-derived from abalone hemocyanin not only enhances survival resilience against paraquat-induced oxidative stress but also rescues proteotoxicity-mediated behavioral deficits in C. elegans, indicating its capacity against stress and neurodegeneration. Interestingly, AbaPep#07 is also found to increase cost-free longevity and age-related physical fitness in nematodes. We then demonstrate that AbaPep#07 can promote nuclear localization of SKN-1/Nrf, but not DAF-16/FOXO, transcription factor. In contrast to its effects in wild-type nematodes, AbaPep#07 cannot increase oxidative stress survival and physical motility in loss-of-function skn-1 mutant, suggesting an SKN-1/Nrf-dependent fashion of these effects. Further investigation reveals that AbaPep#07 can induce transcriptional activation of immune defense, lipid metabolism, and metabolic detoxification pathways, including many SKN-1/Nrf target genes. Together, our findings demonstrate that AbaPep#07 is able to boost stress resilience and reduce behavioral frailty via SKN-1/Nrf-governed transcriptional reprogramming, and provide an insight into the health-promoting potential of antioxidant cryptides as geroprotectors in aging and associated conditions.

Exploration of risk analysis and elimination methods for a Cr(VI)-removal recombinant strain through a biosafety assessment in mice.

Though recombinant strains are increasingly recognized for their potential in heavy metal remediation, few studies have evaluated their safety. Moreover, biosafety assessments of fecal-oral pathway exposure at country as well as global level have seldom analyzed the health risks of exposure to microorganisms from a microscopic perspective. The present study aimed to predict the long-term toxic effects of recombinant strains by conducting a subacute toxicity test on the chromium-removal recombinant strain 3458 and analyzing the gut microbiome. The available disinfection methods were also evaluated. The results showed that strain 3458 induced liver damage and affected renal function and lipid metabolism at 1.0 × 1011 CFU/mL, which may be induced by its carrier strain, pET-28a. Strain 3458 poses the risk of increasing the number of pathogenic bacteria under prolonged exposure. When 500 mg L-1 chlorine-containing disinfectant or 250 mg L-1 chlorine dioxide disinfectant was added for 30 min, the sterilization rate exceeded 99.9 %. These findings suggest that existing wastewater disinfection methods can effectively sterilize strain 3458, ensuring its application value. The present study can serve a reference for the biosafety evaluation of the recombinant strain through exposure to the digestive tract and its feasibility for application in environmental pollution remediation.

Therapeutic targeting of mitochondria-proteostasis axis by antioxidant polysaccharides in neurodegeneration.

Aging is a major risk factor for many age-associated disorders, including neurodegenerative diseases. Both mitochondrial dysfunction and proteostatic decline are well-recognized hallmarks of aging and age-related neurodegeneration. Despite a lack of therapies for neurodegenerative diseases, a number of interventions promoting mitochondrial integrity and protein homeostasis (proteostasis) have been shown to delay aging-associated neurodegeneration. For example, many antioxidant polysaccharides are shown to have pharmacological potentials in Alzheimer's, Parkinson's and Huntington's diseases through regulation of mitochondrial and proteostatic pathways, including oxidative stress and heat shock responses. However, how mitochondrial and proteostatic mechanisms work together to exert the antineurodegenerative effect of the polysaccharides remains largely unexplored. Interestingly, recent studies have provided a growing body of evidence to support the crosstalk between mitostatic and proteostatic networks as well as the impact of the crosstalk on neurodegeneration. Here we summarize the recent progress of antineurodegenerative polysaccharides with particular attention in the mitochondrial and proteostatic context and provide perspectives on their implications in the crosstalk along the mitochondria-proteostasis axis.

Physicochemical characterization and cosmetic application of kelp blanching water polysaccharides.

Seaweeds account for half of global mariculture and have become a key player in bio-based industries. Seaweed process typically starts with hot water blanching that helps reduce postharvest quality deterioration but also generates large amounts of hydrothermal waste. This study aims to explore the feasibility of isolating water-soluble biopolymers from seaweed hydrothermal waste and their potential applications. Using Saccharina japonica (formerly Laminaria japonica) blanching water as example, 2.9 g/L of polymeric substances were efficiently isolated by ultrafiltration, implying biopolymer coproduction potential of ~5.8 kt from blanching wastewater of current kelp industry. Physicochemical characterizations revealed polysaccharidic nature of the biopolymers, with high contents of fucose, uronic acids and sulfate, showing distinct but also overlapping structural features with hot water-extracted kelp polysaccharides. The main fraction of the blanching water polymers after anion exchange chromatography was acidic polysaccharide, the major backbone residues of which were (1-4) linked mannopyranose, (1-4) linked gulopyranose and (1-2) linked fucopyranose while the branched residues were primarily 1,3,4-, 1,2,4- and 1,4,6-linked hexoses but also 1,3,4-fucopyranose. Furthermore, the polysaccharides were found to have a good compatibility in cosmetic creams with added cohesiveness and freshness, demonstrating the application potential of such natural biopolymers from currently underexplored seaweed blanching water.

Clinical implication and immunological landscape analyses of ANLN in pan-cancer: A new target for cancer research.

BACKGROUND: Anillin is a F-actin binding protein (ANLN) mainly involved in the process of cytokinesis and known to be dysregulated in diverse cancers. However, the role of ANLN in pan-cancer prognosis and tumor immunity remains unclear. METHODS: Gene expression profiles of 31 solid tumors were downloaded from The Cancer Genome Atlas (TCGA) database. ANLN mRNA and protein expression were quantified using quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC). Protein expression of ANLN was further confirmed in Human Protein Atlas (HPA) database. Cox regression and Kaplan-Meier analysis were utilized to assess the prognostic value of ANLN in pan-cancer. The correlation between ANLN and different immune gene markers and infiltration cells was analyzed via ESTIMATE and CIBERSORT. A BLCA immunotherapy cohort: IMvigor (210) was used to confirm the role of ANLN in immune response. RESULTS: ANLN upregulation was detected in 21 types of cancers and was associated with poor overall survival (OS), disease-free interval (DFI), and progression-free interval (PFI) in most cancers except in THYM (Thymoma). Additionally, correlation analysis revealed a significantly positive association between ANLN expression and tumor mutation burden (TMB), microsatellite instability (MSI), immune cells infiltration. and immune checkpoint genes in various cancers. The BLCA immunotherapy cohort confirmed that patients with higher ANLN level had better immune responses and longer OS. CONCLUSION: ANLN may serve as a prognostic biomarker for pan-cancer. ANLN upregulation is associated with higher TMB, MSI, and immune cell infiltration in multiple types of tumors, shedding new light for cancer treatment.

Integrated Analyses of m6A Regulator-Based Signature on Its Clinical Application and Immunogenomic Landscape in Stomach Adenocarcinoma.

Background: The whole tumor microenvironment (TME) infiltration features monitored by integrated roles of different RNA N6-methyladenosine (m6A) regulators remain elusive. Our study is aimed at exploring the association between m6A modification patterns, TME cell-infiltrating levels, and patients' prognosis in stomach adenocarcinoma (STAD) patients. Methods: Consensus clustering was performed based on the integrated analyses of 17 m6A regulators and 229 m6A-related hallmark genes in STAD (The Cancer Genome Atlas (TCGA) cohort, n = 443; Gene Expression Omnibus (GEO) GSE57303, n = 70, GSE62254 n = 300, and GSE84437 n = 433). A m6ASig scoring system was calculated by the principal component analysis (PCA), and its prognostic value was validated in an independent dataset GES15459. Results: Three m6A clusters were identified among 1246 STAD patients, which had significant overall survival (OS) differences and demonstrated different TME immune cell infiltration and biological behaviors. According to the m6ASig score, which was generated from the m6A-related hallmark genes, STAD patients were divided into the high-m6ASig group (n = 585) and low-m6ASig group (n = 586). Patients in the high-m6ASig group had a notably prolonged OS and higher immune cell infiltration. Moreover, patients with higher m6ASig score were associated with higher microsatellite instability (MSI); higher PD-L1, CTLA4, and ERBB2 expressions; and greater tumor mutation burden (TMB). Patients with higher m6ASig score demonstrated a better immune response and drug sensitivity. Conclusion: Our m6ASig scoring system could characterize TME immune cell infiltration, thus predict patient's prognosis and immunotherapy and chemotherapy efficacy, offering a novel tool for the individualized therapeutic implications for STAD patients.

Caenorhabditis elegans as an emerging model in food and nutrition research: importance of standardizing base diet.

As a model organism that has helped revolutionize life sciences, Caenorhabditis elegans has been increasingly used in nutrition research. Here we explore the tradeoffs between pros and cons of its use as a dietary model based primarily on literature review from the past decade. We first provide an overview of its experimental strengths as an animal model, focusing on lifespan and healthspan, behavioral and physiological phenotypes, and conservation of key nutritional pathways. We then summarize recent advances of its use in nutritional studies, e.g. food preference and feeding behavior, sugar status and metabolic reprogramming, lifetime and transgenerational nutrition tracking, and diet-microbiota-host interactions, highlighting cutting-edge technologies originated from or developed in C. elegans. We further review current challenges of using C. elegans as a nutritional model, followed by in-depth discussions on potential solutions. In particular, growth scales and throughputs, food uptake mode, and axenic culture of C. elegans are appraised in the context of food research. We also provide perspectives for future development of chemically defined nematode food ("NemaFood") for C. elegans, which is now widely accepted as a versatile and affordable in vivo model and has begun to show transformative potential to pioneer nutrition science.

IL7R Is Correlated With Immune Cell Infiltration in the Tumor Microenvironment of Lung Adenocarcinoma.

Tumor microenvironment plays an important role in the development, progression, and prognosis of lung adenocarcinoma. Exploring new biomarkers based on the immune microenvironment of lung adenocarcinoma can effectively predict the prognosis and provide effective clinical treatment. In this study, we used the ESTIMATE algorithm to score the immune and stromal components in lung adenocarcinoma data downloaded from the TCGA database. The result showed that the immune/stromal score was associated with clinical features and prognosis of lung adenocarcinoma patients. Interleukin-7 receptor (IL7R) is an important prognostic biomarker identified by intersection analysis of protein-protein interaction networks and Cox regression survival analysis. According to TCGA and Oncomine database analysis, IL7R expression in adenocarcinoma tissues was significantly lower than that in normal lung tissues and was further verified in clinical tissue samples. Survival analysis showed IL7R was an independent prognostic factor of lung adenocarcinoma. IL7R expression was positively correlated with the overall survival and progression-free survival of lung adenocarcinoma patients and negatively correlated with tumor size. Our results suggest that IL7R inhibits tumor growth by regulating the proportion of immune infiltrating cells in the tumor immune microenvironment. IL7R could be a beneficial prognostic marker in patients with lung adenocarcinoma and has great potential in immune therapy.

Identification of polyphenols from Rosa roxburghii Tratt pomace and evaluation of in vitro and in vivo antioxidant activity.

Rosa roxburghii Tratt pomace (RRTP) has increasingly attracted attention due to its various nutritional ingredients and health benefits. In this study, the free phenolic fraction (RRTP-FPF) and bound phenolic fraction (RRTP-BPF) were extracted from RRTP by solvent extraction method and alkaline hydrolysis method, respectively. The composition of polyphenols in RRTP-FPF and RRTP-BPF were identified by ultra-high performance liquid chromatography equipped with an electrospray ionization and quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS/MS). In vitro antioxidant assays indicated that RRTP-FPF and RRTP-BPF could scavenge radicals in a dose-dependent manner, and RRTP-BPF exhibited better scavenging activity than RRTP-FPF. In addition, RRTP-FPF and RRTP-BPF (20 âˆ¼ 100 µg/mL) treatment for 24 h could significantly increase the survival rate and decrease reactive oxygen species (ROS) level of paraquat-exposed nematodes through improving the activities of superoxide dismutase (SOD) and catalase (CAT). These results suggest that RRTP could be as a good and cheap source of natural antioxidants.

Caenorhabditis elegans as a Model System for Discovering Bioactive Compounds Against Polyglutamine-Mediated Neurotoxicity.

Age-related misfolding and aggregation of pathogenic proteins are responsible for several neurodegenerative diseases. For example, Huntington's disease (HD) is principally driven by a CAG nucleotide repeat that encodes an expanded glutamine tract in huntingtin protein. Thus, the inhibition of polyglutamine (polyQ) aggregation and, in particular, aggregation-associated neurotoxicity is a useful strategy for the prevention of HD and other polyQ-associated conditions. This paper introduces generalized experimental protocols to assess the neuroprotective capacity of test compounds against HD using established polyQ transgenic Caenorhabditis elegans models. The AM141 strain is chosen for the polyQ aggregation assay as an age-associated phenotype of discrete fluorescent aggregates can be easily observed in its body wall at the adult stage due to muscle-specific expression of polyQ::YFP fusion proteins. In contrast, the HA759 model with strong expression of polyQ-expanded tracts in ASH neurons is used to examine neuronal death and chemoavoidance behavior. To comprehensively evaluate the neuroprotective capacity of target compounds, the above test results are ultimately presented as a radar chart with profiling of multiple phenotypes in a manner of direct comparison and direct viewing.

Sea Cucumber-Derived Peptides Alleviate Oxidative Stress in Neuroblastoma Cells and Improve Survival in C. elegans Exposed to Neurotoxic Paraquat.

Oxidative stress results when the production of oxidants outweighs the capacity of the antioxidant defence mechanisms. This can lead to pathological conditions including cancer and neurodegeneration. Consequently, there is considerable interest in compounds with antioxidant activity, including those from natural sources. Here, we characterise the antioxidant activity of three novel peptides identified in protein hydrolysates from the sea cucumber Apostichopus japonicus. Under oxidative stress conditions, synthetic versions of the sea cucumber peptides significantly compensate for glutathione depletion, decrease mitochondrial superoxide levels, and alleviate mitophagy in human neuroblastoma cells. Moreover, orally supplied peptides improve survival of the Caenorhabditis elegans after treatment with paraquat, the latter of which leads to the production of excessive oxidative stress. Thus, the sea cucumber peptides exhibit antioxidant activity at both the cellular and organism levels and might prove attractive as nutritional supplements for healthy ageing.

Antioxidant and antiaging effect of traditional Thai rejuvenation medicines in Caenorhabditis elegans.

OBJECTIVE: This study explored the rejuvenation mechanisms of Thai polyherbal medicines using different approaches, including in vitro methods, as well as a well-defined nematode model, Caenorhabditis elegans. METHODS: THP-R-SR012 decoction was selected from 23 polyherbal medicines, based on metal-chelating and chain-breaking antioxidant capacities. The influences of this extract on the survival and some stress biomarkers of C. elegans under paraquat-induced oxidative stress were evaluated. Furthermore, lifespan analysis and levels of lipofuscin accumulation were examined in senescent nematodes. The phytochemical profile of THP-R-SR012 was analyzed. RESULTS: Supplementation with THP-R-SR012 decoction significantly increased the mean lifespan and reduced the oxidative damage to C. elegans under oxidative stress conditions. Further, THP-R-SR012 supplementation slightly influenced the lifespan and the level of lipofuscin accumulation during adulthood. Antioxidant-related phytochemical constituents of THP-R-SR012 decoction were rutin, naringenin, 3,4-dihydroxybenzoic acid, gallic acid, glycyrrhizic acid, demethoxycurcumin and 18α-glycyrrhetinic acid. CONCLUSION: The antioxidant potential of THP-R-SR012 was due to its scavenging properties, its enhancement of antioxidant-related enzyme activities, and the presence of the antioxidant-related compound. These results support the traditional use of THP-R-SR012 decoction as a tonic for nourishing and strengthening the whole body.

Enzymatic preparation of Crassostrea oyster peptides and their promoting effect on male hormone production.

ETHNOPHARMACOLOGICAL RELEVANCE: Crassostrea gigas Thunberg and other oysters have been traditionally used in China as folk remedies to invigorate the kidney and as natural aphrodisiacs to combat male impotence. AIM OF THE STUDY: Erectile dysfunction (ED) has become a major health problem for the global ageing population. The aim of this study is therefore to evaluate the effect of peptide-rich preparations from C. gigas oysters on ED and related conditions as increasing evidence suggests that peptides are important bioactive components of marine remedies and seafood. MATERIALS AND METHODS: Crassostrea oyster peptide (COP) preparations COP1, COP2 and COP3 were obtained from C. gigas oysters by trypsin, papain or sequential trypsin-papain digestion, respectively. The contents of testosterone, cyclic adenosine monophosphate (cAMP) and nitric oxide (NO) and the activity of nitric oxide synthase (NOS) in mice and/or cells were measured by enzyme-linked immunosorbent assays. Real-time PCR was used to assess the expression of genes associated with sex hormone secretion pathways. The model animal Caenorhabditis elegans was also used to analyze the gene expression of a conserved steroidogenic enzyme. In silico analysis of constituent peptides was performed using bioinformatic tools based on public databases. RESULTS: The peptide-rich preparation COP3, in which >95% peptides were <3000 Da, was found to increase the contents of male mouse serum testosterone and cAMP, both of which are known to play important roles in erectile function, and to increase the activity of mouse penile NOS, which is closely associated with ED. Further investigation using mouse Leydig-derived TM3 cells demonstrates that COP3 was able to stimulate the production of testosterone as well as NO, a pivotal mediator of penile erection. Real-time PCR analysis reveals that COP3 up-regulated the expression of Areg and Acvr2b, the genes known to promote sex hormone secretion, but not Fst, a gene involved in suppressing follicle-stimulating hormone release. Furthermore, COP3 was also shown to up-regulate the expression of let-767, a well-conserved C. elegans gene encoding a protein homologous to human 17-ß-hydroxysteroid dehydrogenases. Preliminary bioinformatic analysis using the peptide sequences in COP3 cryptome identified 19 prospective motifs, each of which occurred in more than 10 peptides. CONCLUSIONS: In this paper, Crassostrea oyster peptides were prepared by enzymatic hydrolysis and were found for the first time to increase ED-associated biochemical as well as molecular biology parameters. These results may help to explain the ethnopharmacological use of oysters and provide an important insight into the potentials of oyster peptides in overcoming ED-related health issues.

MicroRNA profiling in serum: Potential signatures for breast cancer diagnosis.

BACKGROUND: Circulating microRNAs (miRNAs) prove to be potential non-invasive indicators of cancers. The purpose of this study is to profile serum miRNA expression in breast cancer (BC) patients to find potential biomarkers for BC diagnosis. METHODS: The miRNA expression patterns of serum samples from 216 BC patients and 214 normal control subjects were compared. A four-phase validation was conducted for biomarker identification. In the screening phase, the Exiqon miRNA qPCR panel was employed to select candidates, which were further analyzed by quantitative reverse transcriptase PCR in the following training, testing, and external validation phases. RESULTS: A 12-miRNA (let-7b-5p, miR-106a-5p, miR-19a-3p, miR-19b-3p, miR-20a-5p, miR-223-3p, miR-25-3p, miR-425-5p, miR-451a, miR-92a-3p, miR-93-5p, and miR-16-5p) panel in serum was constructed. The diagnostic performance of the panel was assessed using ROC curve analyses. The area under the curves (AUCs) were 0.952, 0.956, 0.941 and 0.950 for the four separate phases, respectively. Additionally, the expression features of the 12 miRNAs were further explored in 32 pairs of BC tumor and para-tumor tissues, and 32 pairs of serum exosomes samples from patients and healthy subjects. miR-16-5p, miR-106a-5p, miR-25-3p, miR-425-5p, and miR-93-5p were highly overexpressed and let-7b-5p was conversely downregulated in tumor tissues. Excluding miR-20a-5p and miR-223-3p, the 10 other miRNAs were all significantly upregulated in BC serum-derived exosomes. CONCLUSION: A signature consisting of 12 serum miRNAs was identified and showed potential for use in non-invasive diagnosis of BC.

Antioxidant and anti-aging effects of a sea cucumber protein hydrolyzate and bioinformatic characterization of its composing peptides.

Sea cucumbers have been used as food delicacies and traditional medicine for centuries, and their health benefits are partly attributed to their repertoire of proteins. Peptides prepared from the sea cucumber Apostichopus japonicus are reported to have in vitro antioxidant activities. Here, we investigated the in vivo antioxidant capacity of AjPH, a peptide-rich A. japonicus protein hydrolyzate, and found that AjPH is capable of increasing the survival rate and reducing the reactive oxygen species (ROS) level in the animal model Caenorhabditis elegans under increased oxidative stress induced by paraquat. AjPH is also shown to enhance the antioxidant defense system in paraquat-exposed nematodes, including upregulation of superoxide dismutase and catalase activities and reduction of malondialdehyde contents. To explore underpinning antioxidant mechanisms, cellular and chemical assays were used to demonstrate that AjPH not only reduces ROS accumulation in cells but also directly scavenges DPPH free radicals. Further studies indicate that AjPH can decrease age pigments and extend lifespan but does not reduce food intake, body length and brood size of the nematodes, demonstrating its capacity to delay physiological aging. Using activity-guided fractionation by ultrafiltration and gel filtration, we then isolated antioxidant fractions from AjPH and identified the sequences of their composing peptides, which were subjected to in silico analysis for prospective motifs, physicochemical properties and antioxidant potential. Taken together, our results provide an insight into the nutraceutical potential of the sea cucumber protein hydrolyzate for aging and related conditions and also a basis for future mechanistic studies of individual antioxidant peptides.

The Traditional Formula Kai-Xin-San Alleviates Polyglutamine-Mediated Neurotoxicity by Modulating Proteostasis Network in Caenorhabditis elegans.

The inherited polyglutamine (polyQ) expansion diseases are characterized by progressive accumulation of aggregation-prone polyQ proteins, which may provoke proteostasis imbalance and result in significant neurotoxicity. Using polyQ transgenic Caenorhabditis elegans models, we find that Kai-Xin-San (KXS), a well-known herbal formula traditionally used to treat mental disorders in China, can alleviate polyQ-mediated neuronal death and associated chemosensory deficiency. Intriguingly, KXS does not reduce polyQ aggregation in vitro as demonstrated by Thioflavin-T test, but does inhibit polyQ aggregation in C. elegans models, indicating an indirect aggregation-inhibitory mechanism. Further investigation reveals that KXS can modulate two key arms of the protein quality control system, that is, heat shock response and autophagy, to clear polyQ aggregates, but has little effect on proteasome activity. In addition, KXS is able to reduce oxidative stress, which is involved in proteostasis and neurodegeneration, but has no effect on life span or dietary restriction response. To examine potential interaction of the four component herbs of KXS, a dissection strategy was used to study the effects of differential herbal combinations in C. elegans polyQ models. While the four herbs do contribute additively to KXS function, Panax ginseng is found to be the most effective constituent. Taken together, these findings not only demonstrate the neuroprotective ability of KXS but also suggest its potential as a proteostasis regulator in protein aggregation disorders and provide an insight into the mechanism studies of traditionally used complex prescriptions and their rationality.