Impact of Molecular Weight Variations in Dendrobium officinale Polysaccharides on Antioxidant Activity and Anti-Obesity in Caenorhabditis elegans.

This research investigates the impact of Dendrobium officinale polysaccharides (DOP) with different molecular weights on antioxidant effects, lifespan enhancement, and obesity reduction, utilizing both in vitro analyses and the Caenorhabditis elegans (C. elegans) model. Through a series of experiments-ranging from the extraction and modification of polysaccharides, Gel Permeation Chromatography (GPC), and analysis of composition to the evaluation of antioxidant capabilities, this study thoroughly examines DOP and its derivatives (DOP5, DOP15, DOP25) produced via H2O2-Fe2+ degradation. The results reveal a direct relationship between the molecular weight of polysaccharides and their bioactivity. Notably, DOP5, with its intermediate molecular weight, demonstrated superior antioxidant properties, significantly extended the lifespan, and improved the health of C. elegans. Furthermore, DOP15 appeared to regulate lipid metabolism by affecting crucial lipid metabolism genes, including fat-4, fat-5, fat-6, sbp-1, and acs-2. These findings highlight the potential application of DOP derivatives as natural antioxidants and agents against obesity, contributing to the development of functional foods and dietary supplements.

Terpenoids derived from Semen Ziziphi Spinosae oil enhance sleep by modulating neurotransmitter signaling in mice.

Semen Ziziphi Spinosae oil (SZSO) is a natural vegetable oil extracted from Semen Ziziphi Spinosae, a traditional Chinese medicine renowned for its sleep-promoting properties, while the mechanisms are still unclear. Our findings revealed that the terpenoids present in SZSO (T-SZSO) were identified as the active components responsible for promoting sleep. Network pharmacological analysis suggested that T-SZSO targeted different sleep-aid pathways to varying degrees and exhibited potential for preventing central nervous system diseases. Notably, lupeol and betulinicaldehyde exhibited more pronounced effects. Additionally, T-SZSO significantly elevated serotonin levels, enhanced gamma-aminobutyric acid (GABA) synthesis, promoted GABA A receptor expression, and decreased glutamate and norepinephrine expression levels. Moreover, T-SZSO was found to downregulate IL-1ß expression while upregulating superoxide dismutase and inducible nitric oxide synthase levels. In conclusion, this study presents the first investigation into the pharmacological basis of SZSO in promoting sleep and highlights the potential of nature food in improving suboptimal health conditions.

Potential association factors for developing effective peptide-based cancer vaccines.

Peptide-based cancer vaccines have been shown to boost immune systems to kill tumor cells in cancer patients. However, designing an effective T cell epitope peptide-based cancer vaccine still remains a challenge and is a major hurdle for the application of cancer vaccines. In this study, we constructed for the first time a library of peptide-based cancer vaccines and their clinical attributes, named CancerVaccine (https://peptidecancervaccine.weebly.com/). To investigate the association factors that influence the effectiveness of cancer vaccines, these peptide-based cancer vaccines were classified into high (HCR) and low (LCR) clinical responses based on their clinical efficacy. Our study highlights that modified peptides derived from artificially modified proteins are suitable as cancer vaccines, especially for melanoma. It may be possible to advance cancer vaccines by screening for HLA class II affinity peptides may be an effective therapeutic strategy. In addition, the treatment regimen has the potential to influence the clinical response of a cancer vaccine, and Montanide ISA-51 might be an effective adjuvant. Finally, we constructed a high sensitivity and specificity machine learning model to assist in designing peptide-based cancer vaccines capable of providing high clinical responses. Together, our findings illustrate that a high clinical response following peptide-based cancer vaccination is correlated with the right type of peptide, the appropriate adjuvant, and a matched HLA allele, as well as an appropriate treatment regimen. This study would allow for enhanced development of cancer vaccines.

Vitamin B12 and folate decrease inflammation and fibrosis in NASH by preventing syntaxin 17 homocysteinylation.

BACKGROUND & AIMS: Several recent clinical studies have shown that serum homocysteine (Hcy) levels are positively correlated, while vitamin B12 (B12) and folate levels are negative correlated, with non-alcoholic steatohepatitis (NASH) severity. However, it is not known whether hyperhomocysteinemia (HHcy) plays a pathogenic role in NASH. METHODS: We examined the effects of HHcy on NASH progression, metabolism, and autophagy in dietary and genetic mouse models, patients, and primates. We employed vitamin B12 (B12) and folate (Fol) to reverse NASH features in mice and cell culture. RESULTS: Serum Hcy correlated with hepatic inflammation and fibrosis in NASH. Elevated hepatic Hcy induced and exacerbated NASH. Gene expression of hepatic Hcy-metabolizing enzymes was downregulated in NASH. Surprisingly, we found increased homocysteinylation (Hcy-lation) and ubiquitination of multiple hepatic proteins in NASH including the key autophagosome/lysosome fusion protein, Syntaxin 17 (Stx17). This protein was Hcy-lated and ubiquitinated, and its degradation led to a block in autophagy. Genetic manipulation of Stx17 revealed its critical role in regulating autophagy, inflammation and fibrosis during HHcy. Remarkably, dietary B12/Fol, which promotes enzymatic conversion of Hcy to methionine, decreased HHcy and hepatic Hcy-lated protein levels, restored Stx17 expression and autophagy, stimulated ß -oxidation of fatty acids, and improved hepatic histology in mice with pre-established NASH. CONCLUSIONS: HHcy plays a key role in the pathogenesis of NASH via Stx17 homocysteinylation. B12/folate also may represent a novel first-line therapy for NASH. LAY SUMMARY: The incidence of non-alcoholic steatohepatitis, for which there are no approved pharmacological therapies, is increasing, posing a significant healthcare challenge. Herein, based on studies in mice, primates and humans, we found that dietary supplementation with vitamin B12 and folate could have therapeutic potential for the prevention or treatment of non-alcoholic steatohepatitis.

The effects of loving-kindness and compassion meditation on life satisfaction: A systematic review and meta-analysis.

Loving-kindness and compassion meditation (LKCM) was a promising intervention for improving life satisfaction, but previous findings have been inconsistent. The current study provides a systematic review and meta-analysis, including 23 empirical studies on LKCM with life satisfaction as an outcome variable. The primary meta-analysis indicated that LKCM significantly enhanced life satisfaction in pre-post design (g = 0.312, k = 15, n = 451), but the significance disappeared in the additional meta-analysis based on randomized controlled trials (g = 0.106, k = 6, n = 404). Moderator analyses found significant effects for type of control (i.e., the effects of LKCM were inferior to active control group, but superior to waitlist condition), but not for other moderators (i.e., participant type, previous meditation experience, specific protocol, components of LKCM, combination with mindfulness mediation, and intervention length). Narrative review identified self-compassion and positive emotions as important mediators. The practice time of LKCM had indirect but not direct association with life satisfaction. The findings supported that LKCM is promising in increasing life satisfaction, but more studies are needed to investigate the effects with more rigorous designs. Future studies should investigate other potential mechanisms and clarify whether LKCM change the reality or the perception of life.

Changes of Serum Ferritin, Hemoglobin, and Serum Iron (SI) and Treatment Effect of Iron Proteinsuccinylate Oral Solution Combined with Vitamin A and D Drops on Children with Nutritional Iron Deficiency Anemia.

OBJECTIVE: The purpose was to evaluate the treatment effect of iron proteinsuccinylate oral solution combined with vitamin A and D drops on children with nutritional iron deficiency anemia. METHODS: 124 children treated in the outpatient department of our hospital from January 2017 to January 2020 were selected as the study subjects. They were randomly divided into control and observation two groups. The control group was treated with iron proteinsuccinylate oral solution (1.5 mL/kg) in the morning and evening, respectively. The observation group received adjuvant treatment with oral vitamin A and D drops based on the treatment of the control group. The treatment effect of proteinsuccinylate oral solution combined with vitamin A and D drops was evaluated by the serum iron (SI), serum ferritin (SF), and transferrin (TRF) levels, the values of CD3+, CD4+, and CD4+/CD8+, and other evaluation indicators. RESULTS: After treatment, the SI and SF levels of children in both groups significantly increased (P < 0.01) while the TRF level significantly decreased (P < 0.01), and the SI and SF levels in the observation group increased more significantly, and the TRF level decreased more significantly compared with those in the control group (P < 0.01). After treatment, the values of CD3+, CD4+, and CD4+/CD8+ of children in both groups significantly increased compared with those before treatment (P < 0.01), and the values of CD3+, CD4+, and CD4+/CD8+ increased more significantly in the observation group compared with those in the control group (P < 0.01). In addition, the evaluation results of treatment effect showed that the markedly effective rate in the observation group was significantly higher than that in the control group (P < 0.01). CONCLUSION: Iron proteinsuccinylate oral solution combined with vitamin A and D drops can better improve the anemia symptoms in children, with high application value.

Novel target capture DNA library preparation method using CircLigase-mediated hook ligation.

Target capture DNA library preparation methods primarily use the biotin-streptavidin interaction to enrich target DNA, requiring complex operations and a time-consuming workflow with a series of wash steps at regulated temperatures. Here, a new method is presented termed 'hook ligation' for target DNA library preparation, using CircLigase to capture target DNA. The concept was validated by library preparation, sequencing, and acquisition of target DNA fragment information through bioinformatics analysis. An efficient reference point for single-strand DNA ligation to a hook sequence using CircLigase is also provided and it is shown that the efficiency can be influenced by the length and the position of the complementary area on the target DNA.

Managing Cancer and Living Meaningfully (CALM) Intervention on Chemotherapy-Related Cognitive Impairment in Breast Cancer Survivors.

Objective: To evaluate the effectiveness and feasibility of Managing Cancer and Living Meaningfully (CALM), which is used to reduce chemotherapy-related cognitive impairment (CRCI), relieve psychological distress, and improve quality of life (QOL) in Chinese breast cancer survivors (BCs). Methods: Seventy-four BCs were enrolled in this study. All patients were randomly assigned to either the CALM group or the care as usual (CAU) group. All patients were evaluated by the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog), Distress Thermometer (DT), and the Functional Assessment of Cancer Therapy-Breast (FACT-B) before and after CALM or CAU application to BCs with CRCI. We compared the differences in all these scores between the CALM group and the control group and analyzed the correlation between cognitive function and QOL. Results: Compared with the CAU group, the performance of the CALM group on the FACT-Cog, DT, and FACT-B showed significant differences before and after CALM (t = -18.909, -5.180, -32.421, P = .000, .000, .000, respectively). Finally, there was a positive correlation between cognitive function and QOL in breast cancer patients before (r = 0.579, P = .000) and after (r = 0.797, P = .000) treatment. Conclusions: The present results indicated that CALM has salutary effects on the improvement of cognitive impairment and QOL and relieves psychological distress in breast cancer patients, which may be due to a positive correlation between psychological distress and cognitive function or QOL.

Structural modulation of gut microbiota reveals Coix seed contributes to weight loss in mice.

Coix seed (CS) is widely used as food material and herbal medicine in Asian countries with hypolipidemic and anti-inflammatory properties. But whether CS takes effect by modulating the composition of the gut microbiota remains unknown. Here, three groups of mice were fed different diets for 5 weeks: standard chow, high fat (HF), and CS added to HF. As compared to chow, mice in HF group demonstrated a significant increase in body weight (BW), fat mass (FM), together with total cholesterol (TC), and they even developed impaired glucose tolerance. These HF-mediated deleterious metabolic effects were counteracted partly by complementing CS. 16S rRNA gene sequencing analysis revealed CS increased the abundance of genera Lactobacillus, Coprococcus, and Akkermansia in the gut microbita, and it also enriched species Akkermansia muciniphila and Lactobacillus agilis. A. muciniphila was reported to be inversely associated with obesity, diabetes and cardiometabolic diseases, while L. agilis was negatively associated with TC, BW, FM and blood glucose in our data. We identified CS-altered microbial metabolic pathways that were linked to Glycerolipid metabolism, Biosynthesis of unsaturated fatty acids, sulfur reduction, and glutathione transport system. Our results indicate CS may be used as prebiotic agents to lose weight and prevent obesity-related metabolic disorders.

Effect of heat stress on production and in-vitro antioxidant activity of polysaccharides in Ganoderma lucidum.

Ganoderma lucidum is a traditional Chinese medicine, and its polysaccharides possess diverse and significant pharmacological activities. This study aimed to investigate the polysaccharide production, molecular characteristics and in-vitro antioxidant activity of G. lucidum fruiting body after the mushroom was harvested and treated with heat stress (HS). HS enhanced the production of polysaccharides after harvest and treatment of 42 °C HS for 2 h, and that resulted in the highest polysaccharide yield of 10.50%, which was 45.63% higher than that of the control, while 37, 45 °C HS had no significant effect on the production. In terms of molecular characteristics, 42 °C HS significantly changed monosaccharide ratio of polysaccharides, but no apparent molecular weight and functional group changes were found in polysaccharides after HS treatment. The results of in-vitro antioxidant activity assay revealed that 42 °C HS significantly improved the antioxidant activities of polysaccharides at the concentration of 2 mg/mL. In conclusion, this study provides a promising strategy to improve the production of G. lucidum fruiting body polysaccharides.

Low-Boron Tolerance Strategies Involving Pectin-Mediated Cell Wall Mechanical Properties in Brassica napus.

Boron (B) is an essential micronutrient for the growth and development of plants. Oilseed rape (Brassica napus L.) is a staple oleaginous crop, which is greatly susceptible to B deficiency. Significant differences in tolerance of low-B stresses are observed in rapeseed genotypes, but the underlying mechanism remains unclear, particularly at the single-cell level. Here we provide novel insights into pectin-mediated cell wall (CW) mechanical properties implicated in the differential tolerance of low B in rapeseed genotypes. Under B deficiency, suspension cells of the low-B-sensitive genotype 'W10' showed more severely deformed morphology, lower viabilities and a more easily ruptured CW than those of the low-B-tolerant genotype 'QY10'. Cell rupture was attributed to the weakened CW mechanical strength detected by atomic force microscopy; the CW mechanical strength of 'QY10' was reduced by 13.6 and 17.4%, whereas that of 'W10' was reduced by 29.0 and 30.4% under 0.25 and 0.10 µM B conditions, respectively. The mechanical strength differences between 'QY10' and 'W10' were diminished after the removal of pectin. Further, 'W10' exhibited significantly higher pectin concentrations with much more rhamnogalacturonan II (RG-II) monomer, and also presented obviously higher mRNA abundances of pectin biosynthesis-related genes than 'QY10' under B deficiency. CW regeneration was more difficult for protoplasts of 'W10' than for those of 'QY10'. Taking the results together, we conclude that the variations in pectin-endowed CW mechanical properties play key roles in modulating the differential genotypic tolerance of rapeseed to low-B stresses at both the single-cell and the plant level, and this can potentially be used as a selection trait for low-B-tolerant rapeseed breeding.

In silico modeling on ADME properties of natural products: Classification models for blood-brain barrier permeability, its application to traditional Chinese medicine and in vitro experimental validation.

In silico modeling of blood-brain barrier (BBB) permeability plays an important role in early discovery of central nervous system (CNS) drugs due to its high-throughput and cost-effectiveness. Natural products (NP) have demonstrated considerable therapeutic efficacy against several CNS diseases. However, BBB permeation property of NP is scarcely evaluated both experimentally and computationally. It is well accepted that significant difference in chemical spaces exists between NP and synthetic drugs, which calls into doubt on suitability of available synthetic chemical based BBB permeability models for the evaluation of NP. Herein poor discriminative performance on BBB permeability of NP are first confirmed using internal constructed and previously published drug-derived computational models, which warrants the need for NP-oriented modeling. Then a quantitative structure-property relationship (QSPR) study on a NP dataset was carried out using four different machine learning methods including support vector machine, random forest, Naïve Bayes and probabilistic neural network with 67 selected features. The final consensus model was obtained with approximate 90% overall accuracy for the cross-validation study, which is further taken to predict passive BBB permeability of a large dataset consisting of over 10,000 compounds from traditional Chinese medicine (TCM). For 32 selected TCM molecules, their predicted BBB permeability were evaluated by in vitro parallel artificial membrane permeability assay and overall accuracy for in vitro experimental validation is around 81%. Interestingly, our in silico model successfully predicted different BBB permeation potentials of parent molecules and their known in vivo metabolites. Finally, we found that the lipophilicity, the number of hydrogen bonds and molecular polarity were important molecular determinants for BBB permeability of NP. Our results suggest that the consensus model proposed in current work is a reliable tool for prioritizing potential CNS active NP across the BBB, which would accelerate their development and provide more understanding on their mechanisms, especially those with pharmacologically active metabolites.

Sensitive detection of mercury and copper ions by fluorescent DNA/Ag nanoclusters in guanine-rich DNA hybridization.

In this work, we designed a new fluorescent oligonucleotides-stabilized silver nanoclusters (DNA/AgNCs) probe for sensitive detection of mercury and copper ions. This probe contains two tailored DNA sequence. One is a signal probe contains a cytosine-rich sequence template for AgNCs synthesis and link sequence at both ends. The other is a guanine-rich sequence for signal enhancement and link sequence complementary to the link sequence of the signal probe. After hybridization, the fluorescence of hybridized double-strand DNA/AgNCs is 200-fold enhanced based on the fluorescence enhancement effect of DNA/AgNCs in proximity of guanine-rich DNA sequence. The double-strand DNA/AgNCs probe is brighter and stable than that of single-strand DNA/AgNCs, and more importantly, can be used as novel fluorescent probes for detecting mercury and copper ions. Mercury and copper ions in the range of 6.0-160.0 and 6-240 nM, can be linearly detected with the detection limits of 2.1 and 3.4 nM, respectively. Our results indicated that the analytical parameters of the method for mercury and copper ions detection are much better than which using a single-strand DNA/AgNCs.

[Litter decomposition of dominant plantations in Guangxi and its effects on leachate quality].

To understand the decomposition characteristics of the litters in different forest plantations and the effects of released substances during litter decomposition on the leachate quality, litter samples (leaf, shoot, and cortices) were collected from five forest plantations (1 year-old Eucalyptus urophylla x E. grandis, EU1; 4 year-old Eucalyptus urophylla x E. grandis, EU4; 7 year-old Acacia mangium x A. auriculaef, AM; 13 year-old Pinus massoniana Lamb, PL; and mixed broad-leaved softwood, BL), and incubated at 28 degrees C, using water leached for 255 days. In the first 105 days, the litter leachates of EU1 and EU4 had significantly higher coloration and N and P contents and lower pH than those of AM, PL, and BL. On the 255th day, the cumulative chemical oxygen demand (COD) in the leaf litters leachates of EU1 and EU4 was 193.9 and 212.8 g x kg(-1), being 4.2, 4.0, and 4.3 times and 5.3, 4.4, and 4.7 times higher than that of AM, PL, and BL, respectively. The mass loss rate and the N and P leaching rate of the leaf litter of EU1 were significantly higher than those of AM, PL, and BL. The mass loss rate of cortices of EU1 was significantly higher than that of PL. No significant difference was observed for the leaching rate of the shoot litters between AM, PL, and BL. Among the litter samples, leaf litter was easiest to be decomposed, while shoot litter was most difficult to be decomposed. The pH value of the litter leachates of Eucalyptus plantations was significantly negatively correlated with leachate chroma and COD, and the COD had significant positive correlations with the concentrations of total N and P in the leachates.

Systematic assessment of reduced representation bisulfite sequencing to human blood samples: A promising method for large-sample-scale epigenomic studies.

Complementary to the time- and cost-intensive direct bisulfite sequencing, we applied reduced representation bisulfite sequencing (RRBS) to the human peripheral blood mononuclear cells (PBMC) from YH, the Asian individual whose genome and epigenome has been deciphered in the YH project and systematically assessed the genomic coverage, coverage depth and reproducibility of this technology as well as the concordance of DNA methylation levels measured by RRBS and direct bisulfite sequencing for the detected CpG sites. Our result suggests that RRBS can cover more than half of CpG islands and promoter regions with a good coverage depth and the proportion of the CpG sites covered by the biological replicates reaches 80-90%, indicating good reproducibility. Given a smaller data quantity, RRBS enjoys much better coverage depth than direct bisulfite sequencing and the concordance of DNA methylation levels between the two methods is high. It can be concluded that RRBS is a time and cost-effective sequencing method for unbiased DNA methylation profiling of CpG islands and promoter regions in a genome-wide scale and it is the method of choice to assay certain genomic regions for multiple samples in a rapid way.

Atorvastatin ameliorates experimental autoimmune neuritis by decreased Th1/Th17 cytokines and up-regulated T regulatory cells.

Statins have anti-inflammatory and immune-regulating properties. To investigate the effects of atorvastatin on experimental autoimmune neuritis (EAN), an animal model of Guillain-Barré syndrome (GBS), atorvastatin was administered to Lewis rats immunized with bovine peripheral myelin in complete Freund's adjuvant. We found that atorvastatin ameliorated the clinical symptoms of EAN, decreased the numbers of inflammatory cells as well as IFN-γ(+) and IL-17(+) cells in sciatic nerves, decreased the CD80 expression and increased the number of CD25(+)Foxp3(+) cells in mononuclear cells (MNC), and decreased the levels of IFN-γ in MNC culture supernatants. These data provide strong evidence that atorvastatin can act as an inhibitor in EAN by inhibiting the immune response of Th1 and Th17, decreasing the expression of co-stimulatory molecule, and up-regulating the number of T regulatory cells. These data demonstrated that statins could be used as a therapeutic strategy in human GBS in future.

Whole genome DNA methylation analysis based on high throughput sequencing technology.

There are numerous approaches to decipher a whole genome DNA methylation profile ("methylome"), each varying in cost, throughput and resolution. The gold standard of these methods, whole genome bisulfite-sequencing (BS-seq), involves treatment of DNA with sodium bisulfite combined with subsequent high throughput sequencing. Using BS-seq, we generated a single-base-resolution methylome in human peripheral blood mononuclear cells (in press). This BS-seq map was then used as the reference methylome to compare two alternative sequencing-based methylome assays (performed on the same donor of PBMCs): methylated DNA immunoprecipitation (MeDIP-seq) and methyl-binding protein (MBD-seq). In our analysis, we found that MeDIP-seq and MBD-seq are complementary strategies, with MeDIP-seq more sensitive to highly methylated, high-CpG densities and MDB-seq more sensitive to highly methylated, moderate-CpG densities. Taking into account the size of a mammalian genome and the current expense of sequencing, we feel 3gigabases (Gbp) 45bp paired-end MeDIP-seq or MBD-seq uniquely mapped reads is the minimum requirement and cost-effective strategy for methylome pattern analysis.

Ancient human genome sequence of an extinct Palaeo-Eskimo.

We report here the genome sequence of an ancient human. Obtained from approximately 4,000-year-old permafrost-preserved hair, the genome represents a male individual from the first known culture to settle in Greenland. Sequenced to an average depth of 20x, we recover 79% of the diploid genome, an amount close to the practical limit of current sequencing technologies. We identify 353,151 high-confidence single-nucleotide polymorphisms (SNPs), of which 6.8% have not been reported previously. We estimate raw read contamination to be no higher than 0.8%. We use functional SNP assessment to assign possible phenotypic characteristics of the individual that belonged to a culture whose location has yielded only trace human remains. We compare the high-confidence SNPs to those of contemporary populations to find the populations most closely related to the individual. This provides evidence for a migration from Siberia into the New World some 5,500 years ago, independent of that giving rise to the modern Native Americans and Inuit.

Receptor protein tyrosine phosphatase alpha signaling is involved in androgen depletion-induced neuroendocrine differentiation of androgen-sensitive LNCaP human prostate cancer cells.

The neuroendocrine (NE) cells represent the third cell population in the normal prostate. Results of several clinical studies strongly indicate that the NE cell population is greatly increased in prostate carcinomas during androgen ablation therapy that correlates with hormone-refractory growth and poor prognosis. However, the mechanism of NE cell enrichment in prostate carcinoma remains an enigma. We investigated the molecular mechanism by which androgen-sensitive C-33 LNCaP human prostate cancer cells become NE-like cells in an androgen-reduced environment, mimicking clinical phenomenon. In the androgen-depleted condition, androgen-sensitive C-33 LNCaP cells gradually acquired the NE-like morphology and expressed an increased level of neuron-specific enolase (NSE), a classical marker of neuronal cells. Several NE-like subclone cells were established. Biochemical characterizations of these subclone cells showed that receptor-type protein-tyrosine phosphatase alpha (RPTPalpha) is elevated and ERK is constitutively activated, several folds higher than that in parental cells. In androgen-depleted condition, PD98059, an MEK inhibitor, could efficiently block not only the activation of ERK, but also the acquisition of the NE-like morphology and the elevation of NSE in C-33 LNCaP cells. In RPTPalpha cDNA-transfected C-33 LNCaP cells, ERK was activated and NSE was elevated. In those cells in the presence of PD98059, the ERK activation and NSE elevation were abolished, following a dose-response fashion. Additionally, in constitutively active MEK mutant cDNA-transfected C-33 LNCaP cells, ERK was activated and NSE level was elevated, and cells obtained the NE-like phenotype. Our data collectively indicated that RPTPalpha signaling via ERK is involved in the NE transdifferentiation of androgen-sensitive C-33 LNCaP human prostate cancer cells in the androgen-depleted condition.