Integral characterization of normal and alopecic hair at different degeneration stages by in-situ visible and chemical imaging.

Direct exploration to differences between normal hair (NH) and alopecic hair (AH) at different degeneration stages is still lacking. To reveal compositional and structural variation of AH with reference to NH internally and externally, infrared spectroscopic imaging combined with scanning electron microscopy was applied to investigate integral changes of hair chemical profiles and surface texture structures, and infrared macro-fingerprinting analysis revealed detailed chemical compositions of NH and AH. Results showed that AH had excessive irregular laminated structures compared to NH, leading to a lower weight bearing capacity. Spatial distributions of lipids, phosphates, lipoproteins and phospholipids in hair transverse sections showed that their infrared absorptions were intensified and gradually centralized to medulla with average variable-areas increasing upto 2.3 folds (lipoproteins area changed from 13% in NH to 30% in AH)as the alopecia progressed. Extracted pixel spectra from the chemical images showed different fingerprint characteristics in 1075-1120 cm-1. Specifically, compared to NH, AH showed red shift of phosphate peaks, indicating the occurrence of phosphates transformation. In this study, in-situ visible and infrared chemical imaging directly revealed more irregular laminated scalps with decreasing weight bearing capacity and increasing distributive areas expanding to medulla of key components (phosphates, phospholipids, etc.) that were relevant to alopecia development from NH to AH, and offered a fast, eco-friendly and effective method for hair research.

Tylophorine Analog DCB-3503 Inhibited Cyclin D1 Translation through Allosteric Regulation of Heat Shock Cognate Protein 70.

Tylophorine analog DCB-3503 is a potential anticancer and immunosuppressive agent that suppresses the translation of cellular regulatory proteins, including cyclin D1, at the elongation step. However, the molecular mechanism underlying this phenomenon remains unknown. This study demonstrates that DCB-3503 preferentially binds to heat shock cognate protein 70 (HSC70), which is a determinant for cyclin D1 translation by binding to the 3'-untranslated region (3' UTR) of its mRNA. DCB-3503 allosterically regulates the ATPase and chaperone activities of HSC70 by promoting ATP hydrolysis in the presence of specific RNA binding motifs (AUUUA) of cyclin D1 mRNA. The suppression of cyclin D1 translation by DCB-3503 is not solely caused by perturbation of the homeostasis of microRNAs, although the microRNA processing complex is dissociated with DCB-3503 treatment. This study highlights a novel regulatory mechanism of protein translation with AUUUA motifs in the 3' UTR of mRNA by HSC70, and its activity can be allosterically modulated by DCB-3503. DCB-3503 may be used to treat malignancies, such as hepatocellular carcinoma or breast cancer with elevated expression of cyclin D1.

[The effect of combination of glycine and methylprednisolone on Kupffer cells of liver after hemorrhagic shock in rats].

OBJECTIVE: To investigate the effect of combination of glycine and methylprednisolone (MP) on Kupffer cells in liver of rats suffered from hemorrhagic shock. METHODS: Fifty Wistar rats were bled to establish the shock model and subsequently resuscitated with shed blood and normal saline. Just prior to resuscitation, the rats were randomly assigned to 5 groups: sham group, shock group, shock + glycine group, shock + MP group and shock + glycine + MP group. The intracellular calcium concentration and the level of tumor necrosis factor alpha (TNF alpha) in the culture medium of Kupffer cells were determined after stimulation with different concentrations (1, 10, 100 and 1000 ng/ml) of lipopolysaccharide (LPS). RESULTS: Concentration of intracellular calcium and production of TNF-alpha by isolated Kupffer cells stimulated by LPS were elevated significantly in the rats with hemorrhagic shock, which were totally prevented by glycine + MP compared with other groups (P < 0.005). CONCLUSIONS: The combination of glycine and MP prevents the increase of intracellular calcium of Kupffer cell, suppress Kupffer cell activation, decrease the production of TNF-alpha of Kupffer cell and block systemic inflammatory responses more effectively than single administer of glycine or MP.

[Effects of hypercapnia on nuclear factor-kappaB and TNF-alpha in acute lung injury models].

AIM: To observe the effects of hypercapnia on nuclear factor-kappaB and TNF-alpha in acute lung injury models. METHODS: Six of the twenty-two healthy New Zealand white rabbits were randomly allocated to control group (Group C), the other sixteen rabbits were injected with oleic acid (0.1 ml/kg) intravenously, then were randomized to normocapnic group (Group N, n = 8) versus hypercapnic group (Group H, n = 8). TNF-alpha of serum and bronchoalveolar lavage fluid (BALF) and the expression of nuclear factor-kappaB in the lung were analyzed after three hours' mechanical ventilation. RESULTS: TNF-alpha of serum and bronchoalveolar lavage fluid in Group N and H was significantly higher than that in Group C (P < 0.01), and that of Group N was higher than that of Group H (P < 0.05). The expression of nuclear factor-kappaB in Group H was less than that in Group N by both immunohistochemistry and Western-blot analysis. Peak airway pressure in Group H was significantly lower than that in Group N and the dynamic lung compliance was significantly higher than that in Group N (P < 0.05). PaO2 in Group H was significantly higher than that in Group N (P < 0.05). Histologic damage in Group N was significantly severer than that in Group H. CONCLUSION: Hypercapnia is protective in this in vivo model of ALl. The mechanisms might be associated with the prohibition of nuclear factor-kappaB and then the decreased expression of TNF-alpha by hypercapnia.