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.

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.

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.

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.

Food-Derived Antioxidant Polysaccharides and Their Pharmacological Potential in Neurodegenerative Diseases.

Oxidative stress is known to impair architecture and function of cells, which may lead to various chronic diseases, and therefore therapeutic and nutritional interventions to reduce oxidative damages represent a viable strategy in the amelioration of oxidative stress-related disorders, including neurodegenerative diseases. Over the past decade, a variety of natural polysaccharides from functional and medicinal foods have attracted great interest due to their antioxidant functions such as scavenging free radicals and reducing oxidative damages. Interestingly, these antioxidant polysaccharides are also found to attenuate neuronal damages and alleviate cognitive and motor decline in a range of neurodegenerative models. It has recently been established that the neuroprotective mechanisms of polysaccharides are related to oxidative stress-related pathways, including mitochondrial function, antioxidant defense system and pathogenic protein aggregation. Here, we first summarize the current status of antioxidant function of food-derived polysaccharides and then attempt to appraise their anti-neurodegeneration activities.

Astragalus Polysaccharide Suppresses 6-Hydroxydopamine-Induced Neurotoxicity in Caenorhabditis elegans.

Astragalus membranaceus is a medicinal plant traditionally used in China for a variety of conditions, including inflammatory and neural diseases. Astragalus polysaccharides are shown to reduce the adverse effect of levodopa which is used to treat Parkinson's disease (PD). However, the neuroprotective effect of Astragalus polysaccharides per se in PD is lacking. Using Caenorhabditis elegans models, we investigated the protective effect of astragalan, an acidic polysaccharide isolated from A. membranaceus, against the neurotoxicity of 6-hydroxydopamine (6-OHDA), a neurotoxin that can induce parkinsonism. We show that 6-OHDA is able to degenerate dopaminergic neurons and lead to the deficiency of food-sensing behavior and a shorter lifespan in C. elegans. Interestingly, these degenerative symptoms can be attenuated by astragalan treatment. Astragalan is also shown to alleviate oxidative stress through reducing reactive oxygen species level and malondialdehyde content and increasing superoxide dismutase and glutathione peroxidase activities and reduce the expression of proapoptotic gene egl-1 in 6-OHDA-intoxicated nematodes. Further studies reveal that astragalan is capable of elevating the decreased acetylcholinesterase activity induced by 6-OHDA. Together, our results demonstrate that the protective effect of astragalan against 6-OHDA neurotoxicity is likely due to the alleviation of oxidative stress and regulation of apoptosis pathway and cholinergic system and thus provide an important insight into the therapeutic potential of Astragalus polysaccharide in neurodegeneration.

Antioxidant and neuroprotective effects of Dictyophora indusiata polysaccharide in Caenorhabditis elegans.

ETHNOPHARMACOLOGICAL RELEVANCE: Dictyophora indusiata is a medicinal mushroom traditionally used in China for a variety of conditions, including inflammatory and neural diseases. D. indusiata polysaccharides (DiPS) are shown to have in vitro antioxidant activity but in vivo evidence is lacking. This study aimes to explore the antioxidant capacity and related neuroptotective activities of DiPS using wild-type and neurodegenerative Caenorhabditis elegans models. MATERIALS AND METHODS: The antioxidant capacities of DiPS were first determined using paraquat survival and Pgst-4::GFP expression assays in wild-type and transgenic C. elegans models, respectively, and then further investigated by determining reactive oxygen species (ROS) level, malondialdehyde (MDA) content and superoxide dismutase (SOD) activity as well as functional parameters of mitochondria. The activation of stress response transcription factors and neuroptotective activities were examined using nuclear localization and chemosensory behavioral assays in transgenic nematodes, respectively. RESULTS: DiPS was shown not only to increase survival rate and reduce stress level under paraquat-induced oxidative conditions but also to decrease ROS and MDA levels and increase SOD activity in C. elegans models. Moreover, DiPS was also able to restore the functional parameters of mitochondria, including membrane potential and ATP content, in paraquat-stressed nematodes. In addition, nuclear translocation assays demonstrate that the stress response transcription factor DAF-16/FOXO was involved in the antioxidant activity of the polysaccharide. Further experiments reveal that DiPS was capable of reducing ROS levels and alleviating chemosensory behavior dysfunction in transgenic nematode models of neurodegenerative diseases mediated by polyglutamine and amyloid-ß protein. CONCLUSIONS: These findings demonstrate the antioxidant and neuroprotective activities of the D. indusiata polysaccharide DiPS in wild-type and neurodegenerative C. elegans models, and thus provide an important pharmacological basis for the therapeutic potential of D. indusiata in neurodegeneration.

Preclinical Evaluation of an Epidermal Growth Factor Receptor-Targeted Doxorubicin-Peptide Conjugate: Toxicity, Biodistribution, and Efficacy in Mice.

Doxorubicin (DOX) is known to induce apoptosis and necrosis in healthy tissue resulting in unwanted toxicities. To improve the ability of DOX to more specifically target tumors and minimize undesirable side effects, conjugation of DOX with epidermal growth factor receptor (EGFR)--binding peptide (DOX-EBP) has been developed to deliver DOX to EGFR-overexpressing neoplastic cells. Here, we investigated whether DOX-EBP was able to reduce toxicity and enhance anticancer efficacy in vivo through receptor-mediated targeted delivery system. Nude mice were treated with DOX or DOX-EBP to estimate general toxicity, normal tissue damage, biodistribution, and antitumor efficacy. In addition, the expression levels of EGFR in tumor tissues and normal organs were investigated by Western blotting, and their mRNA expression was analyzed by reverse transcription PCR. This study demonstrated that DOX-EBP was able to effectively decrease the distribution of DOX in normal tissues without EGFR overexpressing and reduce DOX-induced toxicity. On the other hand, the research also confirmed that DOX-EBP was able to preferentially accumulate DOX in EGFR-overexpressing tumor tissues and showed the enhanced anticancer efficacy over free DOX. DOX-EBP could be used for receptor-targeted chemotherapy with less toxicity and greater efficacy of tumor cells overexpressing EGFR. DOX-EBP conjugate is a good therapeutic agent for cancer treatment.

Extracts of Tsai Tai (Brassica chinensis): enhanced antioxidant activity and anti-aging effects both in vitro and in Caenorhabditis elegans.

Tsai Tai is one of the most widely consumed Brassica vegetables in Asian countries because of its good taste and its nutritional benefits. This study evaluated the antioxidant capacity and possible associated health benefits of 3 Tsai Tai (Brassica chinensis) varieties, namely, Hon Tsai Tai, Pak Choi and Choi Sum. The DPPH radical scavenging ability and reducing power assays were performed to evaluate the in vitro activities of the extracts. Caenorhabditis elegans was used as an in vivo model for evaluation of beneficial health effects, including antioxidant activity and delayed aging. In vitro, the Hon Tsai Tai extract exhibited higher antioxidant activities than Pak Choi and Choi Sum, and the total phenolic contents were significantly correlated with the DPPH and RP values. In vivo, the three assayed Tsai Tai extracts significantly increased resistance against paraquat-induced oxidative stress with an increase in survival rates from 15% to 28% compared with controls. However, only the extract from Hon Tsai Tai significantly prolonged the lifespan of Caenorhabditis elegans, with an 8% increase in the mean lifespan with respect to controls. Further evidence of antioxidant protection was obtained by assessing ROS production via the DCF assay. The analyses of intracellular SOD activity and MDA content confirmed the existence of an antioxidant protective effect. These results suggest that Tsai Tai might serve as a good source of natural antioxidants, and in particular, Hon Tsai Tai could be explored as a potential dietary supplement to retard aging.

Caenorhabditis elegans in Chinese medicinal studies: making the case for aging and neurodegeneration.

Aging is a progressive process with degenerative changes of various tissues and organs. As a classic model organism in genetics and neurobiology, Caenorhabditis elegans is also a powerful system in aging and behavioral studies and can be used at both the molecular and organismal levels to evaluate potential therapeutics for age-related neurodegeneration, owing to its short life span, relative simplicity, and high degree of experimental tractability as well as significant conservation of disease genes and signaling pathways with humans. We attempt here to summarize the use of C. elegans models in exploring traditional Chinese medicine for potential remedies against aging and neurodegeneration.

Polysaccharides from medicinal herbs as potential therapeutics for aging and age-related neurodegeneration.

Recent studies have uncovered important aging clues, including free radicals, inflammation, telomeres, and life span pathways. Strategies to regulate aging-associated signaling pathways are expected to be effective in the delay and prevention of age-related disorders. For example, herbal polysaccharides with considerable anti-oxidant and anti-inflammation capacities have been shown to be beneficial in aging and age-related neurodegenerative diseases. Polysaccharides capable of reducing cellular senescence and modulating life span via telomere and insulin pathways have also been found to have the potential to inhibit protein aggregation and aggregation-associated neurodegeneration. Here we present the current status of polysaccharides in anti-aging and anti-neurodegenerative studies.

Overview of beverages with anti-aging functions in Chinese market.

Anti-aging Chinese medicines have been used in traditional beverages to promote health and prevent diseases. Interestingly, these functional beverages may be used differently between men and women, reflecting the "yin-yang" philosophy of Chinese medicine. Modern studies have revealed that some dietary natural products can slow aging in model organisms, and functional beverages containing such products have recently emerged in Chinese market, challenging the dominance of traditional functional beverages. Here we summarize both traditional anti-aging herbs and modern natural dietary compounds currently used in functional beverages in China, and also briefly outline the underlying mechanisms of the beverages in slowing aging process.

Ethanolic extract and water-soluble polysaccharide from Chaenomeles speciosa fruit modulate lipopolysaccharide-induced nitric oxide production in RAW264.7 macrophage cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Chaenomeles speciosa fruits have been widely used in traditional Chinese medicine for treatment of diseases related to inflammatory reaction. This study aims to identify anti-inflammatory and immunomodulatory components of Chaenomeles speciosa fruit and unravel their potential mechanisms. MATERIALS AND METHODS: Ethanolic extract and its n-hexane, chloroform, ethyl acetate and n-butanol fractions, as well as water-soluble polysaccharide, were prepared from dry fruits of Chaenomeles speciosa. The mouse macrophage-like RAW264.7 cells were induced by lipopolysaccharide (LPS) and used as an inflammatory cell model. Production of nitric oxide in the cells was determined by the Griess assay, and cell viability was tested by the MTT method. Cellular apoptosis was evaluated by fluorescence-activated cell sorting. Relative quantification of inflammation-related genes was analyzed by real-time PCR. RESULTS: LPS-induced production of nitric oxide in RAW264.7 cells was significantly inhibited by the ethyl acetate fraction (EAF) at 200-800µg/ml, while Chaenomeles speciosa polysaccharide (CPS) promoted nitric oxide production at 250-750µg/ml either alone or in an additive fashion with LPS. Both EAF and CPS did not provoke noticeable cytotoxicity and apoptosis at the above effective concentrations. EAF significantly reduced LPS-induced upshift of iNOS mRNA level but showed no significant effect on the induction of IFN-γ and G-CSF, while CPS reduced the gene induction of TNF-α, IFN-γ and G-CSF by LPS. CONCLUSIONS: EAF was able to inhibit nitric oxide production by reducing LPS-induced upshift of iNOS mRNA level. CPS was an activator of nitric oxide production through cytokines such as TNF-α, IFN-γ and G-CSF. These results demonstrate the therapeutic effects of both ethanolic and aqueous extracts of Chaenomeles speciosa fruit, a traditional edible medicine used in health maintenance and disease treatment.

Autophagy-related gene 7 (ATG7) and reactive oxygen species/extracellular signal-regulated kinase regulate tetrandrine-induced autophagy in human hepatocellular carcinoma.

Tetrandrine, a bisbenzylisoquinoline alkaloid isolated from the broadly used Chinese medicinal herb Stephaniae tetrandrae, exhibits potent antitumor effects and has the potential to be used as a cancer chemotherapeutic agent. We previously reported that high concentrations of tetrandrine induce apoptosis in liver cancer cells. Here, we found that in human hepatocellular carcinoma (HCC) cells, a low dose of tetrandrine (5 µm) induced the expression of LC3-II, resulted in the formation of acidic autophagolysosome vacuoles (AVOs), and caused a punctate fluorescence pattern with the GFP-LC3 protein, which all are markers for cellular autophagy. Tetrandrine induced the production of intracellular reactive oxygen species (ROS), and treatment with ROS scavengers significantly abrogated the tetrandrine-induced autophagy. These results suggest that the generation of ROS plays an important role in promoting tetrandrine-induced autophagy. Tetrandrine-induced mitochondrial dysfunction resulted in ROS accumulation and autophagy. ROS generation activated the ERK MAP kinase, and the ERK signaling pathway at least partially contributed to tetrandrine-induced autophagy in HCC cells. Moreover, we found that tetrandrine transcriptionally regulated the expression of autophagy related gene 7 (ATG7), which promoted tetrandrine-induced autophagy. In addition to in vitro studies, similar results were also observed in vivo, where tetrandrine caused the accumulation of ROS and induced cell autophagy in a tumor xenograft model. Interestingly, tetrandrine treatment also induced autophagy in a ROS-dependent manner in C. elegans muscle cells. Therefore, these findings suggest that tetrandrine is a potent autophagy agonist and may be a promising clinical chemotherapeutic agent.

The neuroprotective and lifespan-extension activities of Damnacanthus officinarum extracts in Caenorhabditis elegans.

AIM OF THE STUDY: This study was aimed to evaluate the neuroprotective and anti-aging activity of extracts in Caenorhabditis elegans from the roots and leaves of Damnacanthus officinarum Huang to provide the pharmacological basis in traditional medicine. MATERIALS AND METHODS: Investigations on the neuroprotective and lifespan activity were carried out, which were observed by utilizing the following models: observing the worms' chemosensory behavior test based on the aversion index in the assay plate, neuroprotective activity of nematode by evaluating the ASH neuron survival and lifespan test in C. elegans. RESULTS: It has been shown that the ethanol, n-butanol and aqueous extracts in the roots possessed significantly neuroprotective effect both in chemosensory behavior test and ASH neuron survival model. The same extracts in the leaves showed similar activities in two models, but have less potency revealing by the data. Four candidate extracts, possessing excellent neuroprotective activity, extend lifespan in C. elegans. The n-butanol extracts in the root part showed best efficacy among them. CONCLUSION: The results show the n-butanol and aqueous extracts are the major pharmacological plant extracts. Moreover, the neuroprotective and lifespan-extension activity effects of root extracts are superior to leave extracts, supporting the traditional application of above-ground parts of DOH in treating various diseases associated with brain disorders and anti-aging.

Macromolecular and small-molecule modulation of intracellular Aß42 aggregation and associated toxicity.

Aß (amyloid ß-peptide) has a central role in AD (Alzheimer's disease) where neuronal toxicity is linked to its extracellular and intracellular accumulation as oligomeric species. Searching for molecules that attenuate Aß aggregation could uncover novel therapies for AD, but most studies in mammalian cells have inferred aggregation indirectly by assessing levels of secreted Aß peptide. In the present study we establish a mammalian cell system for the direct visualization of Aß formation by expression of an Aß(42)-EGFP (enhanced green fluorescent protein) fusion protein in the human embryonic kidney cell line T-REx293, and use this to identify both macromolecules and small molecules that reduce aggregation and associated cell toxicity. Thus a molecular shield protein AavLEA1 [Aphelenchus avenae LEA (late embryogenesis abundant) protein 1], which limits aggregation of proteins with expanded poly(Q) repeats, is also effective against Aß(42)-EGFP when co-expressed in T-REx293 cells. A screen of polysaccharide and small organic molecules from medicinal plants and fungi reveals one candidate in each category, PS5 (polysaccharide 5) and ganoderic acid DM respectively, with activity against Aß. Both PS5 and ganoderic acid DM probably promote Aß aggregate clearance indirectly through the proteasome. The model is therefore of value to study the effects of intracellular Aß on cell physiology and to identify reagents that counteract those effects.

Cyanobacteria-/cyanotoxin-contaminations and eutrophication status before Wuxi drinking water crisis in Lake Taihu, China.

After the appalling "Wuxi Drinking Water Crisis", increasing investigations concerning the contaminations of cyanobacterial blooms and their toxins in Lake Taihu have been performed and reported in the last two years. However, information regarding these issues before the crisis in 2007 remained insufficient. To provide some background data for further comparisons, the present study reported our investigations conducted in 2004, associated with the cyanotoxin contaminations as well as the eutrophication status in Lake Taihu. Results from the one-year-study near a drinking water resource for Wuxi City indicated that, unlike the status in recent two years, cyanobacteria and chlorophyta are the co-dominance species throughout the year. The highest toxin concentration (34.2 ng/mL) in water columns occurred in August. In bloom biomass, the peak value of intracellular toxin (0.59 microg/mg DW) was determined in October, which was lag behind that in water column. In addition, MC-RR was the major toxin variant throughout the year. During the study period, nutrients levels of total nitrogen and phosphorus were also recorded monthly. Results from the present study will lead to a better understanding of the eutrophication status and the potential risks before "Wuxi Drinking Water Crisis".

Cryptobiosis, aging, and cancer: yin-yang balancing of signaling networks.

Some organisms adapt to persistent and severe stress by reversibly adjusting life-death balance to a new equilibrium, e.g., anhydrobiosis ("life without water") enables survival in a quiescent state on extreme desiccation. Aging is characterized by declining response and increasing vulnerability to stress, and the balance slowly, and irreversibly, tilts toward death. Although tumorigenesis tips the balance of cells to prolonged life, paradoxically it can cause organismal death. At the molecular level, all these phenomena involve complex signaling pathways, but it is highly likely that the overall balance of signaling outcomes, rather than individual signals themselves, plays the pivotal role in life-death decisions.