Application of noninvasive sampling technique in mitochondrial genome intraspecific phylogeny of the endangered butterfly, Teinopalpus aureus (Lepidoptera: Papilionidae).

The butterfly genus of Teinopalpus, endemic to Asia, embodies a distinct species of mountain-dwelling butterflies with specific habitat requirements. These species are rare in the wild and hold high conservation and research value. Similar to other protected species, the genetic analysis of the rare Teinopalpus aureus poses challenges due to the complexity of sampling. In this study, we successfully extracted DNA and amplified mitochondrial genomic DNA from various noninvasive sources such as larval feces, larval exuviae, larval head capsules, pupal exuviaes, and filamentous gland secretions, all integral parts of butterfly metamorphosis. This was conducted as part of a research initiative focused on the artificial conservation of T. aureus population in Jinggang Shan Nature Reserve. Our findings illustrated the successful extraction of DNA from multiple noninvasive sources, achieved through modified DNA extraction methodologies. Although the DNA concentration obtained from noninvasive samples was lower than that from muscle tissues of newly dead larvae during rearing, all samples met the requirements for PCR amplification and sequencing, yielding complete circular sequences. These sequences are pivotal for both interspecific and intraspecific genetic relationship analysis. Our methods can be extended to other insects, especially scarce species.

An Au/SnO-SnO2 nanosheet based composite used for rapid detection of hydrogen sulphide.

In this work, a new type of H2S sensor was fabricated by means of drop-coating of an Au/SnO-SnO2 nanosheet material, which was prepared by a one-pot hydrothermal reaction, onto a gold electrode in an alumina ceramic tube with the formation of a thin nanocomposite film. The microstructure and morphology of the nanosheet composites were characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). A gas-sensitivity study presented good H2S-sensing performance of such Au/SnO-SnO2 nanosheet composites. At an optimal operating temperature of 240 °C and ambient temperature of 25 °C, the resulting sensor showed a good linear response to H2S in a range of 1.0 to 100 ppm with a low detection limit of 0.7 ppm, and a very fast response-recovery time of 22 s for response and 63 s for recovery, respectively. The sensor was also unaffected by ambient humidity and had good reproducibility and selectivity. When being applied to the monitoring of H2S in an atmospheric environment in a pig farm, the response signal to H2S was only attenuated by 4.69% within 90 days, proving that the sensor had a long and stable service lifetime for continuous running and showing its important practical application prospects.

ZnO@CuO hollow nanosphere-based composites used for the sensitive detection of hydrogen sulfide with long-term stability.

In this study, zinc oxide@cupric oxide hollow nanospheres (ZnO@CuO HNS, 330 nm in diameter) were successfully prepared by a hard-template method using amino-phenolformaldehyde resin spheres (APF) as the templates. A new type of thin-film gas sensor toward hydrogen sulfide (H2S) was fabricated by means of drop-coating on the gold electrode of an alumina ceramic tube. The microstructure and morphology of the nanosphere composites were characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM), and the gas-sensing performance of the composites toward the detection of H2S were investigated. The ZnO@CuO nanocomposite with a hollow structure exhibited good gas-sensing properties. Under the optimum operating temperature of 260 °C, ambient temperature of 30 °C, and ambient humidity of 70%, the linear response of the sensor to H2S was in the concentration range of 0.1-100 ppm, and its detection limit reached 0.0611 ppm, with a quick response time of 78 s. Also, the sensor possessed good repeatability, selectivity, and stability. The long-term stability and run duration of such sensors were pronounced, with only a 1.9% reduction in the signal after the continuous monitoring of H2S gas in a pig farm for 18 months using Alibaba's cloud remote transmission system, which presents an important practical application prospect in atmosphere environment monitoring on livestock-raising fields.

Exosome-Derived lncRNA NEAT1 Exacerbates Sepsis-Associated Encephalopathy by Promoting Ferroptosis Through Regulating miR-9-5p/TFRC and GOT1 Axis.

Sepsis can cause sepsis-associated encephalopathy (SAE), but whether SAE was induced or exacerbated by ferroptosis remains unknown. In this study, the rat sepsis model was constructed using the cecal ligation and puncture method. The blood-brain barrier (BBB) permeability was measured by Evans blue dye (EBD) in vivo. The levels of ROS, Fe ion, MDA, GSH, and GPX4 were assessed by enzyme-linked immunosorbent assay (ELISA). The exosomes isolated from serum were cultured with bEnd.3 cells for the in vitro analysis. Moreover, bEnd.3 cells cultured with 100 µM FeCl3 (iron-rich) were to simulate ferroptosis stress. The cell viability was evaluated by Cell Counting Kit-8 (CCK-8) assay. A dual-luciferase reporter gene assay was performed to confirm the relationship between miR-9-5p with NEAT1, TFRC, and GOT1. In vivo, it is found that BBB permeability was damaged in model rats. Level of ROS, Fe ion, and MDA was increased, and level of GSH and GPX4 was decreased, which means ferroptosis was induced by sepsis. Exosome-packaged NEAT1 in serum was significantly upregulated in model rats. In vitro, it is found that NEAT1 functions as a ceRNA for miR-9-5p to facilitate TFRC and GOT1 expression. Overexpression of NEAT1 enhanced ferroptosis stress in bEnd.3 cells. Increased miR-9-5p alleviated sepsis-induced ferroptosis by suppressing the expression of TFRC and GOT1 both in vivo and in vitro. In conclusion, these findings suggest that sepsis induced high expression of serous exosome-derived NEAT1, and it might exacerbate SAE by promoting ferroptosis through regulating miR-9-5p/TFRC and GOT1 axis.

Streptococcus thermophilus Inhibits Colorectal Tumorigenesis Through Secreting ß-Galactosidase.

BACKGROUND & AIMS: Streptococcus thermophilus was identified to be depleted in patients with colorectal cancer (CRC) by shotgun metagenomic sequencing of 526 multicohort fecal samples. Here, we aim to investigate whether this bacterium could act as a prophylactic for CRC prevention. METHODS: The antitumor effects of S thermophilus were assessed in cultured colonic epithelial cells and in 2 murine models of intestinal tumorigenesis. The tumor-suppressive protein produced by S thermophilus was identified by mass spectrometry and followed by ß-galactosidase activity assay. The mutant strain of S thermophilus was constructed by homologous recombination. The effect of S thermophilus on the gut microbiota composition was assessed by shotgun metagenomic sequencing. RESULTS: Oral gavage of S thermophilus significantly reduced tumor formation in both Apcmin/+ and azoxymethane-injected mice. Coincubation with S thermophilus or its conditioned medium decreased the proliferation of cultured CRC cells. ß-Galactosidase was identified as the critical protein produced by S thermophilus by mass spectrometry screening and ß-galactosidase activity assay. ß-Galactosidase secreted by S thermophilus inhibited cell proliferation, lowered colony formation, induced cell cycle arrest, and promoted apoptosis of cultured CRC cells and retarded the growth of CRC xenograft. The mutant S thermophilus without functional ß-galactosidase lost its tumor-suppressive effect. Also, S thermophilus increased the gut abundance of known probiotics, including Bifidobacterium and Lactobacillus via ß-galactosidase. ß-Galactosidase-dependent production of galactose interfered with energy homeostasis to activate oxidative phosphorylation and downregulate the Hippo pathway kinases, which partially mediated the anticancer effects of S thermophilus. CONCLUSION: S thermophilus is a novel prophylactic for CRC prevention in mice. The tumor-suppressive effect of S thermophilus is mediated at least by the secretion of ß-galactosidase.

Heterologous Boosting With Listeria-Based Recombinant Strains in BCG-Primed Mice Improved Protection Against Pulmonary Mycobacterial Infection.

While Baccillus Calmette-Guerin (BCG) is used worldwide, tuberculosis (TB) is still a global concern due to the poor efficacy of BCG. Novel vaccine candidates are therefore urgently required. In this study, two attenuated recombinant Listeria strains, LMΔ-msv and LIΔ-msv were constructed by deletion of actA and plcB and expression of a fusion protein consisting of T cell epitopes from four Mycobacterium tuberculosis (Mtb) antigens (Rv2460c, Rv2660c, Rv3875, and Rv3804c). The safety and immunogenicity of the two recombinant strains were evaluated in C57BL/6J mice. After intravenous immunization individually, both recombinant strains entered liver and spleen but eventually were eliminated from these organs after several days. Simultaneously, they induced antigen-specific cell-mediated immunity, indicating that the recombinant Listeria strains were immunogenic and safe in vivo. LMΔ-msv immunization induced stronger cellular immune responses than LIΔ-msv immunization, and when boosted with LIΔ-msv, antigen-specific IFN-γ CD8+ T cell responses were notably magnified. Furthermore, we evaluated the protection conferred by the vaccine candidates against mycobacterial infection via challenging the mice with 1 × 107 CFU of BCG. Especially, we tested the feasibility of application of them as heterologous BCG supplement vaccine by immunization of mice with BCG firstly, and boosted with LMΔ-msv and LIΔ-msv sequentially before challenging. Combination immune strategy (LMΔ-msv prime-LIΔ-msv boost) conferred comparable protection efficacy as BCG alone. More importantly, BCG-vaccinated mice acquired stronger resistance to Mycobacterial challenge when boosted with LMΔ-msv and LIΔ-msv sequentially. Our results inferred that heterologous immunization with Listeria-based recombinant strains boosted BCG-primed protection against pulmonary mycobacterial infection.

Comparison of Donepezil, Memantine, Melatonin, and Liuwei Dihuang Decoction on Behavioral and Immune Endocrine Responses of Aged Senescence-Accelerated Mouse Resistant 1 Mice.

Aging is a natural biological process associated with cognitive decline and neuroendocrine-immune system changes; the neuroendocrine-immune system plays crucial role in brain aging and neurodegeneration, and it is essential to discern beneficial attempts to delay the aging progress based on immunological aging. In this study, we have investigated the effects of Traditional Chinese Medicine (TCM)-Liuwei Dihuang decoction (LW)-and donepezil, memantine, and melatonin on cognitive decline in aging mice. The aged SAMR1 mice received oral administration of donepezil (1mg/kg), memantine (10 mg/kg), melatonin (10 mg/kg), and LW (10 g/kg) for 3 months. A shuttle box, Morris water maze, and elevated-zero maze were performed to assess cognitive function, and flowcytometry, Luminex, and radioimmunoassay were performed to measure the lymphocyte subsets, inflammatory factors, and hormones. We observed that survival days of mice was increased with melatonin and LW, the anxiety behavior was significantly improved by memantine, melatonin, and LW treatment, active avoidance responses significantly improved by LW, donepezil, and memantine, the spatial learning ability was significantly improved by donepezil, and LW and melatonin were beneficial to the spatial memory of old mice. For immune function, LW increased CD4+ and CD4+CD28+ cells and reduced TNF-α, IL-1ß, and G-CSF in plasma, and it also promoted the secretion of anti-inflammatory factors IL-4, IL-5, and IL-10 by regulating the active of Th2 cells in spleen. Donepezil and memantine exerted protective effects against CD4+CD28+ cell decrease caused by aging and reduced the pro-inflammatory factors TNF-α, IL-1ß, and G-CSF in plasma. Melatonin could reverse CD8+CD28+ cell imbalances and increased B cells. For endocrine factors, LW increased TSH levels in the pituitary, and melatonin increased the GH level in blood. Our findings indicated that LW improved the cognitive decline in aging mice, and this might be associated with modulation of the active T cells and HPG axis hormones as well as increasing anti-inflammatory factors. Meanwhile, donepezil and memantine have advantages in regulating adaptive immunity, melatonin has advantages in the regulation of B cells and pituitary hormones, and LW exhibits a better effect on neuroendocrine immune function compared with the others from a holistic point of view. LW might be a potential therapeutic strategy for anti-aging-related syndromes, and it can also provide a value on medication guidance about drug combinations or treatment in clinic.

Active Fraction Combination from Liuwei Dihuang Decoction (LW-AFC) Alleviated the LPS-Induced Long-Term Potentiation Impairment and Glial Cells Activation in Hippocampus of Mice by Modulating Immune Responses.

Neuroinflammation is known as a typical feature associated with many neurodegenerative diseases including Alzheimer's disease (AD) and impairs the synaptic plasticity of the hippocampus. LW-AFC is an active fraction combination being extracted from Liuwei Dihuang decoction, a classic traditional Chinese medicine prescription. This study aimed to investigate the effects of LW-AFC on synaptic plasticity in mice with lipopolysaccharide (LPS) treatment. The results showed that the administration of LPS caused fever and long-term potentiation (LTP) impairment in mice. The pretreatment with LW-AFC had an antipyretic effect on fever and improved the impaired LTP induced by LPS, alleviated the microglia and astrocytes activation in the hippocampus, regulated the abnormal T-lymphocyte subpopulation in the spleen and blood caused by LPS, and reduced the aberrant secretion of cytokines in the brain and plasma. The compounds paeoniflorin, morroniside, and loganic acid in LW-AFC regulated the TNF-α secretion in non-LPS- and LPS-stimulated BV-2 cells. These data suggest that LW-AFC improves the LPS-induced impairment of LTP and alleviates the activation of glial cells in the hippocampus, which might be associated with modulating immune responses.

Toxin-mediated ribosome stalling reprograms the Mycobacterium tuberculosis proteome.

Mycobacterium tuberculosis readily adapts to survive a wide range of assaults by modifying its physiology and establishing a latent tuberculosis (TB) infection. Here we report a sophisticated mode of regulation by a tRNA-cleaving toxin that enlists highly selective ribosome stalling to recalibrate the transcriptome and remodel the proteome. This toxin, MazF-mt9, exclusively inactivates one isoacceptor tRNA, tRNALys43-UUU, through cleavage at a single site within its anticodon (UU↓U). Because wobble rules preclude compensation for loss of tRNALys43-UUU by the second M. tuberculosis lysine tRNA, tRNALys19-CUU, ribosome stalling occurs at in-frame cognate AAA Lys codons. Consequently, the transcripts harboring these stalled ribosomes are selectively cleaved by specific RNases, leading to their preferential deletion. This surgically altered transcriptome generates concomitant changes to the proteome, skewing synthesis of newly synthesized proteins away from those rich in AAA Lys codons toward those harboring few or no AAA codons. This toxin-mediated proteome reprogramming may work in tandem with other pathways to facilitate M. tuberculosis stress survival.

Serine and one-carbon metabolism, a bridge that links mTOR signaling and DNA methylation in cancer.

Mammalian / mechanistic target of rapamycin (mTOR) is a critical sensor of environmental cues that regulates cellular macromolecule synthesis and metabolism in eukaryotes. DNA methylation is the most well-studied epigenetic modification that is capable of regulating gene transcription and affecting genome stability. Both dysregulation of mTOR signaling and DNA methylation patterns have been shown to be closely linked to tumor progression and serve as promising targets for cancer therapy. Although their respective roles in tumorigenesis have been extensively studied, whether molecular interplay exists between them is still largely unknown. In this review, we provide a brief overview of mTOR signaling, DNA methylation as well as related serine and one-carbon metabolism, one of the most critical aspects of metabolic reprogramming in cancer. Based on the latest understanding regarding the regulation of metabolic processes by mTOR signaling as well as interaction between metabolism and epigenetics, we further discuss how serine and one-carbon metabolism may serve as a bridge that links mTOR signaling and DNA methylation to promote tumor growth. Elucidating their relationship may provide novel insight for cancer therapy in the future.

A Bifunctional Luminescent Metal-Organic Framework for the Sensing of Paraquat and Fe3+ Ions in Water.

The hydrothermal reaction of Zn2+ ions with a mixture of two ligands, Hcptpy and H3 btc (Hcptpy=4-(4-carboxyphenyl)-2,2':4',4''-terpyridine; H3 btc=1,3,5-benzenetricarboxylic acid), led to the formation of a 3D metal-organic framework (MOF) with 1D channels, [Zn2 (cptpy)(btc)(H2 O)]n (1), which was structurally characterized by using single-crystal X-ray diffraction (SXRD). In MOF 1, two independent Zn2+ ions were interconnected by btc3- ligands to form a 1D chain, whilst adjacent Zn2+ ions were alternately bridged by cptpy- ligands to generate a 2D sheet, which was further linked by 1D chains to form a 3D framework with a new (3,3,4,4)-connected topology. Furthermore, compound 1 also exhibited excellent stability towards air and water and, more importantly, luminescence experiments indicated that it could serve as a probe for the sensitive detection of paraquat (PAQ) and Fe3+ ions in aqueous solution.

Accurate target identification for Mycobacterium tuberculosis endoribonuclease toxins requires expression in their native host.

The Mycobacterium tuberculosis genome harbors an unusually high number of toxin-antitoxin (TA) systems. These TA systems have been implicated in establishing the nonreplicating persistent state of this pathogen during latent tuberculosis infection. More than half of the M. tuberculosis TA systems belong to the VapBC (virulence associated protein) family. In this work, we first identified the RNA targets for the M. tuberculosis VapC-mt11 (VapC11, Rv1561) toxin in vitro to learn more about the general function of this family of toxins. Recombinant VapC-mt11 cleaved 15 of the 45 M. tuberculosis tRNAs at a single site within their anticodon stem loop (ASL) to generate tRNA halves. Cleavage was dependent on the presence of a GG consensus sequence immediately before the cut site and a structurally intact ASL. However, in striking contrast to the broad enzyme activity exhibited in vitro, we used a specialized RNA-seq method to demonstrate that tRNA cleavage was highly specific in vivo. Expression of VapC-mt11 in M. tuberculosis resulted in cleavage of only two tRNA isoacceptors containing the GG consensus sequence, tRNAGln32-CUG and tRNALeu3-CAG. Therefore, our results indicate that although in vitro studies are useful for identification of the class of RNA cleaved and consensus sequences required for accurate substrate recognition by endoribonuclease toxins, definitive RNA target identification requires toxin expression in their native host. The restricted in vivo specificity of VapC-mt11 suggests that it may be enlisted to surgically manipulate pathogen physiology in response to stress.

Prevalence and risk factors of anemia among children aged 6-23 months in Huaihua, Hunan Province.

BACKGROUND: Anemia is one of the most common diseases of childhood and is a health problem globally, particularly in developing counties and in children less than 2 years of age. Anemia during childhood has short- and long-term effects on health. However, few studies have investigated the prevalence of anemia among children in Huaihua. Therefore, this study analyzed the prevalence and risk factors of anemia among children 6 to 23 months of age in Huaihua. METHODS: This cross-sectional study was conducted at a maternal and child health care hospital in Huaihua, from September to November 2017. The study population recruited using a multistage sampling technique. A structured questionnaire was used to collect data on the characteristics of the children and members of their families. Hemoglobin (Hb) levels were measured by using a microchemical reaction method. Logistic regression analysis was used to identify associated factors and odds ratio with 95% CI was computed to assess the strength of association. RESULTS: In total, 4450 children were included in this study. The prevalence of anemia was 29.73%. In multivariate logistic regression analysis, the results show that mother and father of Miao ethnicity (OR = 1.23 and 1.31), diarrhea in the previous 2 weeks (OR = 1.35), breastfeeding in the prior 24 h (OR = 1.50), and caregivers able to identify the optimum timing of complementary feeding (OR = 1.15) had positive correlations with anemia. However, children aged 18 to 23 months (OR = 0.55), father of Dong ethnicity (OR = 0.82), addition of milk powder once or twice (OR = 0.71), addition of infant formula once or twice, three times, and four or more times in the previous 24 h (OR = 0.72, 0.70, and 0.75), and addition of a nutrient sachet four or more times in the prior week (OR = 0.70) were negatively associated with anemia. CONCLUSIONS: The prevalence of anemia among children 6 to 23 months of age in Huaihua was higher than that in more developed regions of China. The feeding practice of caregivers was associated with anemia. nutrition improvement projects are needed to reduce the burden of anemia among children in Huaihua.

MT1G is Silenced by DNA Methylation and Contributes to the Pathogenesis of Hepatocellular Carcinoma.

Using genome-wide screening and TCGA-based data analysis, we identified a DNA methylation-related gene named metallothionein-1G (MT1G), which may play an important role in hepatocellular carcinoma (HCC). In this study, we found that MT1G expression was silenced in 4/6 HCC cell lines and negatively related to aberrant promoter hypermethylation. Its mRNA level was restored with demethylation treatment. Moreover, MT1G downregulation at both the transcriptional and protein level was also detected in 8 pairs of clinical HCC samples compared with its expression in adjacent normal tissues. Ectopic expression of MT1G in silenced HCC cell lines inhibited colony formation, suppressed cell migration and invasion, and repressed xenograft tumor growth in nude mice. In contrast, knockdown of MT1G by short hairpin RNA showed the opposite effect on cell proliferation and the malignant phenotype. Moreover, our data showed that MT1G suppressed tumor invasion and metastasis mainly through regulating the expression of proteins in the matrix metalloproteinase family (MMP) and modulating the epithelial-mesenchymal transition (EMT) process. To our surprise, the data from TCGA showed that hypermethylation of MT1G is associated with good survival of HCC patients. In conclusion, our study demonstrated that MT1G acts as a tumor suppressor gene in HCC development, but its clinical potential in HCC requires further evaluation.

Mitogen-activated protein kinase inhibition enhances the antitumor effects of sporamin in human pancreatic cancer cells.

Sporamin, a sweet potato tuber storage protein, is a Kunitz-type trypsin inhibitor (TI) that has exhibited antitumor activity through poorly defined mechanisms in a number of types of tumor cells. The present study aimed to analyze the combined effects of sporamin and three mitogen-activated protein kinase (MAPK) inhibitors, PD98059, SP600125 and SB203580, on the pancreatic cancer cell line, PANC-1. Cell proliferation activity was assessed using a 3H-thymidine incorporation assay, and cell viability was analyzed using an MTT assay. Apoptosis was assayed by flow cytometry and fluorescence microscopy. Protein expression levels in PANC-1 cells were determined by western blotting. The results of this analysis demonstrated that sporamin induced a temporary increase in the phosphorylation of MAPKs, including phosphorylated extracellular signal regulated-kinase 1/2, phosphorylated c-Jun amino-terminal protein kinase 1/2 and phosphorylated p38-MAPK, in a concentration-dependent manner. However, treatment with MAPK inhibitors promoted the inhibition of cell proliferation and viability, and the induction of apoptosis in sporamin-treated PANC-1 cells. In conclusion, the present study demonstrated that MAPK inhibition enhanced the antitumor activity of sporamin in PANC-1 cells.

Sporamin suppresses growth of human esophageal squamous cell carcinoma cells by inhibition of NF­κB via an AKT­independent pathway.

The aim of the present study was to determine whether sporamin, a trypsin inhibitor, suppresses the growth of human esophageal squamous cell carcinoma (ESCC) cells in vitro. Sporamin treatment led to the suppression of viability and proliferation of human ESCC cell lines, EC9706 and EC109, as determined by MTT and [3H] thymidine incorporation assays, respectively. Flow cytometry and fluorescence microscopy demonstrated that sporamin significantly induced apoptosis in EC9706 and EC109 cells. Western blotting demonstrated that sporamin downregulated the expression of Bcl­2 and Bcl­2 like 1, and upregulated the expression of Bcl­2­associated X in EC9706 and EC109 cells. In addition, marked inhibition of nuclear factor (NF)­κB activation was observed in sporamin­treated EC9706 and EC109 cells by an electrophoretic mobility shift assay. Sporamin treatment also resulted in reduced expression levels of phosphorylated (p)­NF­κB inhibitor α and nuclear NF­κB p65. However, the expression levels of p­protein inase (AKT) and its downstream target, p­p70 S6 kinase, were not markedly altered following sporamin treatment. In conclusion, sporamin may suppress the growth of human ESCC cells via NF­κB­dependent and AKT­independent mechanisms and may act as a promising natural therapeutic agent for the treatment of human ESCC.

p53R2 overexpression in cervical cancer promotes AKT signaling and EMT, and is correlated with tumor progression, metastasis and poor prognosis.

p53R2 is a p53-inducible ribonucleotide reductase subunit involved in deoxyribonucleotide biosynthesis and DNA repair. Although p53R2 has been linked to human cancer, its role in cervical cancer remains unknown. In this study, we investigated the expression and clinical significance of p53R2 in early-stage cervical cancer. p53R2 expression is significantly upregulated at both mRNA and protein levels in cervical cancer cells and tissues, compared with that in matched normal cervical cells and tissues, respectively. p53R2 overexpression is associated with increased risk of pelvic lymph node metastasis (PLNM, p = 0.001) and cancer relapse (p = 0.009). Patients with high p53R2 expression have a shorter overall survival (OS) and disease-free survival (DFS). p53R2 is an independent factor for predicting OS and DFS of cervical cancer patients. We further show that p53R2 is important for oncogenic growth, migration and invasion in cervical cancer cells. Mechanistically, p53R2 promotes Akt signaling and epithelial-mesenchymal transition (EMT). In conclusion, our study demonstrates for the first time that p53R2 protein is overexpressed in early-stage cervical cancer and unravels some unconventional oncogenic functions of p53R2. p53R2 may be a useful prognostic biomarker and therapeutic target for cervical cancer.

LW-AFC Effects on N-glycan Profile in Senescence-Accelerated Mouse Prone 8 Strain, a Mouse Model of Alzheimer's Disease.

Glycosylation is one of the most common eukaryotic post-translational modifications, and aberrant glycosylation has been linked to many diseases. However, glycosylation and glycome analysis is a significantly challenging task. Although several lines of evidence have indicated that protein glycosylation is defective in Alzheimer's disease (AD), only a few studies have focused on AD glycomics. The etiology of AD is unclear and there are no effective disease-modifying treatments for AD. In this study, we found that the object recognition memory, passive avoidance, and spatial learning and memory of senescence-accelerated mouse prone 8 (SAMP8) strain, an AD animal model, were deficient, and LW-AFC, which was prepared from the traditional Chinese medicine prescription Liuwei Dihuang decoction, showed beneficial effects on the deterioration of cognitive capability in SAMP8 mice. Forty-three and 56 N-glycan were identified in the cerebral cortex and serum of SAMP8 mice, respectively. The N-glycan profile in SAMP8 mice was significantly different from that of senescence accelerated mouse resistant 1 (SAMR1) strains, the control of SAMP8 mice. Treatment with LW-AFC modulated the abundance of 21 and 6 N-glycan in the cerebral cortex and serum of SAMP8 mice, respectively. The abundance of (Hex)3(HexNAc)5(Fuc)1(Neu5Ac)1 and (Hex)2(HexNAc)4 decreased in the cerebral cortex and serum of SAMP8 mice compared with SAMR1 mice, decreases that were significantly correlated with learning and memory measures. The administration of LW-AFC could reverse or increase these levels in SAMP8 mice. These results indicated that the effects of LW-AFC on cognitive impairments in SAMP8 mice might be through modulation of N-glycan patterns, and LW-AFC may be a potential anti-AD agent.

LW-AFC, A New Formula Derived from Liuwei Dihuang Decoction, Ameliorates Cognitive Deterioration and Modulates Neuroendocrine-Immune System in SAMP8 Mouse.

BACKGROUND: Alzheimer's disease (AD), the most common cause of dementia among older people, could not be prevented, halted, or reversed up till now. A large body of pharmacological study has revealed that Liuwei Dihuang decoction (LW), a classical traditional Chinese medicinal prescription, possesses potential therapeutic effects on AD. LW-AFC is key fractions from LW. METHOD: Cognition ability was evaluated by behavioral experiments. Using multiplex bead analysis, radioimmunoassay, immunochemiluminometry and ELISA to determine levels of cytokines and hormones. The splenocyte proliferation and peripheral lymphocyte subsets was investigated by 3H-thymidine incorporation and flow cytometric analysis, respectively. RESULTS: This study showed the treatment of LW-AFC slowed the aging process of senescence-accelerated mouse prone 8 strain (SAMP8), a robust model sporadic AD or late-onset/age-related AD. LW-AFC had ameliorative effects on spontaneous locomotor activity, object recognition memory, spatial learning and memory, passive and active avoidance impairment in SAMP8 mice. Administration of LW-AFC restored the imbalance of hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axis, enhanced the proliferation of splenocytes, corrected the disorder of lymphocyte subsets, and regulated the abnormal production of cytokine in SAMP8 mice. Effects of LW-AFC on pharmacodynamics and neuroendocrine immunomodulation network in SAMP8 mice were better than memantine and donepezil. CONCLUSION: This data indicated LW-AFC may be a promising therapeutic medicine for AD.