Gengnianchun, a Traditional Chinese Medicine, Enhances Oxidative Stress Resistance and Lifespan in Caenorhabditis elegans by Modulating

Objective. Gengnianchun (GNC), a traditional Chinese medicine (TCM), is primarily used to improve declining functions related to aging. In this study, we investigated its prolongevity and stress resistance properties and explored the associated regulatory mechanism using a Caenorhabditis elegans model. Methods. Wild-type C. elegans N2 was used for lifespan analysis and oxidative stress resistance assays. Transgenic animals were used to investigate pathways associated with antioxidative stress activity. The effects of GNC on levels of reactive oxygen species (ROS) and expression of specific genes were examined. Results. GNC-treated wild-type worms showed an increase in survival time under both normal and oxidative stress conditions. GNC decreased intracellular ROS levels by 67.95%. GNC significantly enhanced the oxidative stress resistance of several mutant strains, suggesting that the protective effect of GNC is independent of the function of these genes. However, the oxidative stress resistance effect of GNC was absent in worms with daf-16 mutation. We also found upregulation of daf-16 downstream targets including sod-3 and mtl-1. Conclusions. Our findings suggest that GNC extends the lifespan of C. elegans and enhances its resistance to oxidative stress via a daf-16/FOXO-dependent pathway. This study also provides a feasible method for screening the biological mechanisms of TCMs

Histopathologic changes of Reis-Bücklers corneal dystrophy

AIM: To explore the histopathologic changes of Reis-Bücklers corneal dystrophy(RBCD). METHODS: Cornea buttons were obtained from patients in 1 pedigree who underwent lamella keratoplasty. Sections with HE and special staining which included symplectic blue staining and Masson staining and Congo red staining were observed under light microscope. Two normal cornea specimens(donated corneas from eye bank)were used as control. RESULTS: In those patients, the bowman's membrane disappeared. The main lesion was in bowman's membrane through HE staining, positive through PAS Congo red staining and Masson staining, negative through symplectic blue staining.CONCLUSION: The Reis - Bücklers corneal dystrophy is characterized as geographic map-like lesion of bowman's membrane, and the abnormal extracellular deposit is amyloid protein fiber

Effect of Acorus tatarinowii extract on hyperprolactinemia in rats

Purpose: To determine the mechanism underlying the anti-hyperprolactinemia effect of Acorus tatarinowii extract (ATE) in rats. Methods: Rats were divided into six groups (n =10 each group), viz, healthy control, untreated hyperprolactinemic rats, hyperprolactinemic rats treated with bromocriptine (0.6 mg/kg), and hyperprolactinemic rats treated with ATE (3.2, 6.4, or 12.8 g/kg). After 30 days, the hypothalamic protein levels of dopamine D2 receptor, protein kinase A (PKA), and cyclic adenosine monophosphate (cAMP) were determined. Results: Dopamine D2 receptor levels were lower in untreated hyperprolactinemic rats than in healthy control (p < 0.01), but this decrease was attenuated by ATE (p < 0.05). Elevated PKA levels in untreated hyperprolactinemic rats (0.78 ± 0.03µg/mL, p < 0.01) were decreased by ATE (3.2 g/kg, 0.51 ± 0.02 µg/mL, p < 0.05; 6.4 g/kg, 0.39 ± 0.03 µg/mL, p < 0.01; 12.8 g/kg, 0.24 ± 0.04 µg/mL, p < 0.01). Similarly, elevated cAMP levels in hyperprolactinemic rats (3.1 ± 0.3 ng/mL) were lowered by ATE (3.2 g/kg, 2.2 ± 0.4 ng/mL, p < 0.05; 6.4 g/kg, 1.8 ± 0.3 ng/mL, p < 0.01; 12.8 g/kg, 1.4 ± 0.3 ng/mL, p < 0.01). Conclusion: ATE anti-hyperprolactinemia activity is mediated by dopamine D2 receptor signaling via cAMP/PKA pathway

A Chinese Herbal Formula, Gengnianchun, Ameliorates β

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder, and the few drugs that are currently available only treat the symptoms. Traditional medicine or phytotherapy has been shown to protect against AD. In our previous studies, Gengnianchun (GNC), a traditional Chinese medicine formula with a prolongevity effect, protected against Aβ-induced cytotoxicity in pheochromocytoma cells (PC-12 cells) and hippocampal cells. Here, we investigated the effects and possible mechanisms by which GNC protected against Aβ toxicity using transgenic Caenorhabditis elegans CL4176. Our results showed that GNC effectively delayed the Aβ toxicity-triggered body paralysis of CL4176 worms. GNC decreased Aβ by reducing Aβ mRNA levels. Moreover, GNC significantly reduced reactive oxygen species in the AD model worms compared with the controls. In addition, GNC upregulated the daf-16, sod-3, hsp-16.2 genes, and enhanced DAF-16 translocation from the cytoplasm to the nuclei under oxidative stress conditions. GNC treatment of C. elegans strains lacking DAF-16 did not affect the paralysis phenotype. Taken together, these findings suggest that GNC could protect against Aβ-induced toxicity via the DAF-16 pathway in C. elegans. Further studies are required to analyze its effectiveness in more complex animals

miR-15a and miR-16-1 inhibit the proliferation of leukemic cells by down-regulating WT1 protein level

<p>Abstract</p> <p>Background</p> <p>miR-15a and miR-16-1(miR-15a/16-1) have been implicated as tumor suppressors in chronic lymphocytic leukemia, multiple myeloma, and acute myeloid leukemic cells. However the mechanism of inhibiting the proliferation of leukemic cells is poorly understood.</p> <p>Methods</p> <p>K562 and HL-60 cells were transfected with pRS-15/16 or pRS-E, cell growth were measured by CCK-8 assay and direct cell count. Meanwhile WT1 protein and mRNA level were measured by Western blotting and quantitative real-time PCR.</p> <p>Results</p> <p>In this study we found that over-expression of miR-15a/16-1 significantly inhibited K562 and HL-60 cells proliferation. Enforced expression of miR-15a/16-1 in K562 and HL-60 cells significantly reduced the protein level of WT1 but not affected the mRNA level. However enforced expression of miR-15a/16-1 can not reduce the activity of a luciferase reporter carrying the 3'-untranslated region(3'UTR) of WT1. Silencing of WT1 by specific siRNA suppressed leukemic cells proliferation resembling that of miR-15a/16-1 over-expression. Anti-miR-15a/16-1 oligonucleotides (AMO) reversed the expression of WT1 in K562 and HL-60 cells. Finally, we found a significant inverse correlation between miR-15a or miR-16-1 expression and WT1 protein levels in primary acute myeloid leukemia (AML) blasts and normal controls.</p> <p>Conclusions</p> <p>These data suggest that miR-15a/16-1 may function as a tumor suppressor to regulate leukemic cell proliferation potentially by down-regulating the WT1 oncogene. However WT1 is not directly targeted by miR-15a/16-1 through miRNA-mRNA base pairing, therefore more study are required to understand the mechanism by which miR-15a/16-1 downregulate WT1.</p