摘要 :
Alzheimer's disease (AD) is attributable to synapse dysfunction and loss, but the nature and progression of the presynaptic structural and functional changes in AD are essentially unknown. We expressed wild-type or arctic form of ...
展开
Alzheimer's disease (AD) is attributable to synapse dysfunction and loss, but the nature and progression of the presynaptic structural and functional changes in AD are essentially unknown. We expressed wild-type or arctic form of beta amyloid(1-42) (Abeta) in a small group of neurons in the adult fly and performed extensive time course analysis of the function and structure of both axon and presynaptic terminals at the identified single-neuron level. Abeta accumulated intracellularly and induced a range of age-dependent changes, including depletion of presynaptic mitochondria, slowdown of bi-directional transports of axonal mitochondria, decreased synaptic vesicles, increased large vacuoles, and elevated synaptic fatigue. These structural and functional synaptic changes correlated with age-dependent deficit in motor behavior. All these alterations were accelerated in flies expressing the arctic form of Abeta. The depletion of presynaptic mitochondria was the earliest detected phenotype and was not caused by the change in axonal transport of mitochondria. Moreover, axonal mitochondria exhibited a dramatic reduction in number but a significant increase in size in aged Abeta-expressing flies, indicating a global depletion of mitochondria in the neuron and an impairment of mitochondria fission. These results suggest that Abeta accumulation depletes presynaptic and axonal mitochondria, leading to other presynaptic deficits.
收起
摘要 :
OBJECTIVE: autologous chondrocyte implantation usually requires in vitro cell expansion before implantation. We compared the efficacy of cartilage regeneration by in vitro-expanded chondrocytes at high density and freshly harveste...
展开
OBJECTIVE: autologous chondrocyte implantation usually requires in vitro cell expansion before implantation. We compared the efficacy of cartilage regeneration by in vitro-expanded chondrocytes at high density and freshly harvested chondrocytes at low density. DESIGN: surgically created osteochondral defects at weight-bearing surface of femoral condyles of domestic pigs were repaired by biphasic cylindrical porous plugs of DL-poly-lactide-co-glycolide and beta-tricalcium phosphate. Plugs were seeded with autologous chondrocytes in its chondral phase, and press-fit to defects. Seeded cells were (1) in vitro-expanded chondrocytes harvested from stifle joint 3 weeks before implantation and (2) freshly harvested chondrocytes from recipient knee. Seeding densities were 70 x 10(6) and 7 x 10(6) cells/mL, respectively. Cell-free plugs served as control and defects remained untreated as null control. Outcome was examined at 6 months with International Cartilage Repair Society Scale. RESULTS: the two experimental groups were repaired by hyaline cartilage with collagen type II and Safranin-O. Tissue in control group was primarily fibrocartilage. No regeneration was found in null control. Experimental groups had higher mean International Cartilage Repair Society scores than control in surface, matrix, and cell distribution, but were comparable with control in cell viability, subchondral bone, and mineralization. No significant difference existed between two experimental groups in any of the six categories. Uni-axial indentation test revealed similar creeping stress-relaxation property as native cartilage on experimental, but not control, specimen. CONCLUSIONS: cartilage could regenerate in both experimental models, in comparable quality. Culture of chondrocytes before implantation is not necessary.
收起
摘要 :
BACKGROUND: Sorafenib is a newly established cancer drug found to be an effective systemic treatment for advanced hepatocellular carcinoma (HCC). However, little is known about any potential effectors that modify tumor cell sensit...
展开
BACKGROUND: Sorafenib is a newly established cancer drug found to be an effective systemic treatment for advanced hepatocellular carcinoma (HCC). However, little is known about any potential effectors that modify tumor cell sensitivity towards sorafenib. Here, we present the first evidence that glucose-regulated protein 78 (GRP78) is intimately associated with acquisition of resistance towards sorafenib. METHODS: The role of GRP78 in acquisition of resistance towards sorafenib was determined using HepJ5 (a GRP78-overexpressing subline) and HepG2 as its pair-matched control. RNA interference in cancer cells was applied to determine the influence of GRP78 expression on sensitivity to sorafenib treatment. RESULTS: We found that HepG2 cells exhibited higher sensitivity toward sorafenib, with 50% inhibition concentration (IC(50)) >20 microMu for HepJ5 and 4.8 microM for HepG2. Specifically, when HepG2 cells received 20 microM sorafenib treatment for 24 h, over 80% of cells underwent apoptosis compared with only 32% of HepJ5 cells under similar experimental conditions. Similarly, GRP78 knockdown in HepJ5 cells by small interfering RNA (siRNA) technique enhanced the efficacy of sorafenib-mediated cell death. This was reflected by a shift of IC(50) values from >20 microM to 4.8 microM. CONCLUSIONS: GRP78 is a positive modifier for sorafenib resistance acquisition in HCC and represents a prime target for overcoming sorafenib resistance.
收起
摘要 :
Honokiol, a bioactive component isolated from the Chinese herb Magnolia officinalis, is known for its potent antioxidative and anti-inflammatory effects. To study whether honokiol can protect skeletal muscle from sports injuries, ...
展开
Honokiol, a bioactive component isolated from the Chinese herb Magnolia officinalis, is known for its potent antioxidative and anti-inflammatory effects. To study whether honokiol can protect skeletal muscle from sports injuries, we set up an eccentric exercise bout protocol for rats consisting of downhill running on a treadmill and examined the effect of oral administration of honokiol at 1 h before eccentric exercise at a dose of 5 mg/kg on day 1 (HK5 x 1) or 1 mg/kg/day for 5 consecutive days (HK1 x 5). Eccentric exercise was implemented for 3-5 consecutive days, and induced remarkable tissue damage. This damage was associated with an increase in serum creatine levels, increase in protein nitrotyrosylation, poly-ADP-ribose-polymerase (PARP) upregulation, lipid peroxidation, and leukocyte infiltration. The degree of muscle damage also paralleled dramatic gene expression for cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and inflammation-associated cytokines (interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1), possibly through activation of nuclear factor kappa-B (NF-kappaB), a crucial proinflammatory transcription factor. Both honokiol treatments (HK5 x 1 and HK1 x 5) significantly ameliorated eccentric exercise-induced muscle damage as revealed by suppression of cell fragmentation, protein nitrotyrosylation and PARP upregulation, as well as reductions in lipid peroxidation and leukocyte infiltration, possibly through downregulating gene expression for COX-2, iNOS, and the proinflammatory cytokines by modulation of NF-kappaB activation. In conclusion, the present study demonstrates for the first time that honokiol exhibits protective effects against eccentric exercise-induced skeletal muscle damage in rats, probably by modulating inflammation-mediated damage to muscle cells.
收起
摘要 :
An HPLC method permitting the simultaneous determination of fourteen analytes (phenylalkanoids and monoterpenoids) from the roots of Rhodiola rosea was developed. A separation was achieved within 35 min using C(18) column material...
展开
An HPLC method permitting the simultaneous determination of fourteen analytes (phenylalkanoids and monoterpenoids) from the roots of Rhodiola rosea was developed. A separation was achieved within 35 min using C(18) column material and a water-acetonitrile mobile phase, both containing a 0.05% phosphoric acid gradient system and a temperature of 53 degrees C. The method was validated for linearity, repeatability, limits of detection and limits of quantification. The limits of detection and limits of quantification of 14 phenylalkanoids and monoterpenoids were found to be 0.20-1.0 and 0.5-3.5 microg/mL, respectively. The wavelengths used for quantification of phenylalkanoids and monoterpenoids with a diode array detector were 205, 220 and 251 nm. The method was used to analyze the roots of two species of Rhodiola and commercial extracts of R. rosea and provides preliminary evidence of phytochemical differences between North American and Eurasian populations of R. rosea. LC-mass spectrometry coupled with electrospray ionization (ESI) interface method is described for the identification of phenylalkanoids and monoterpenoids in various Rhodiola samples. This method involved the use of the [M + H](+), [M + NH(4)](+) and [M + Na](+) ions in the positive ion mode with extractive ion monitoring (EIM).
收起
摘要 :
We investigated the expression and localization of aquaporin-1 (AQP-1) in hepatitis B virus (HBV)-associated cirrhotic human liver tissues. The expression of AQP-1 at the protein and mRNA levels was analyzed by immunohistochemistr...
展开
We investigated the expression and localization of aquaporin-1 (AQP-1) in hepatitis B virus (HBV)-associated cirrhotic human liver tissues. The expression of AQP-1 at the protein and mRNA levels was analyzed by immunohistochemistry, quantitative real-time polymerase chain reaction (qPCR) and Western blotting in normal and HBV-associated cirrhotic human liver tissues. The correlation with the expression of CK19, CK7 and AQP-1 was also compared. AQP-1 staining was strongly and uniformly positive in mature bile ducts, isolated hepatic progenitor cells (HPCs) and ductular reactions. Scattered intermediate hepatocyte-like cells expressed AQP-1, which are often intimately associated with CK7 positive hepatocytes. However, the number of AQP-1+ intermediate hepatocyte-like cells was lower than that of CK7+ cells, and such positivity was rarely seen on stains for CK19. When compared with normal liver tissues, AQP-1 was overexpressed at both the mRNA and protein levels in the cirrhotic liver tissues. AQP-1 was overexpressed in the cirrhotic liver tissues. AQP-1, similar to CK19, might be a more specific and more sensitive marker than CK7 for the identification of HPCs.
收起
摘要 :
Vocal process granulomas are benign lesions involved in the healing of posterior glottis injuries. Here, we report the results of our conservative treatment of vocal process granulomas. Fifty-three patients with 54 occurrences of ...
展开
Vocal process granulomas are benign lesions involved in the healing of posterior glottis injuries. Here, we report the results of our conservative treatment of vocal process granulomas. Fifty-three patients with 54 occurrences of granulomas between 1998 and 2007 were enrolled. All patients were observed without surgical excision or specific medications and regularly monitored with telescopic examinations until the granulomas disappeared. Data on age, sex, clinical presentation, prior history of intubation or gastroesophageal reflux, telescopic findings, management and clinical course were reviewed. There were 41 males and 12 females. The mean ages of granuloma occurrence were 48.1 years in men and 41.6 years in women (p=0.16). Symptoms included hoarseness in 42 patients, cough in 13 patients, lumping sensation in the throat in 15 patients and sore throat in 14 patients. Ten occurrences were stable during the follow-up period, and the other 44 (81%) achieved complete remission (mean period of 30.6 weeks). The remission patterns included progression and remission in 6 occurrences, slow remission in 22 and rapid remission in 16. The remission rate of granulomas was not significantly related to age (p=0.71), sex (p=0.43), prior intubation (p=0.71), acid reflux (p=0.47), unilateral/bilateral lesions (p=1.00) or granuloma size (p=0.46). The remission time was significantly shorter in patients with prior intubation (p=0.04), but not significantly associated with age (p=0.89), sex (p=0.87), acid reflux (p=0.91), unilateral/bilateral lesions (p=0.26) or granuloma size (p=0.96). Long-term observation has demonstrated that vocal process granulomas can be cured at high remission rates without implementing specific treatments.
收起
摘要 :
The 70 % EtOH extract of Polygonum cuspidatum showed inhibitory action against HIV-1-induced syncytium formation at non-cytotoxic concentrations in vitro with a 50 % effective concentration (EC(50)) of 13.94 +/- 3.41 microg/mL. Th...
展开
The 70 % EtOH extract of Polygonum cuspidatum showed inhibitory action against HIV-1-induced syncytium formation at non-cytotoxic concentrations in vitro with a 50 % effective concentration (EC(50)) of 13.94 +/- 3.41 microg/mL. Through bioactivity-guided fractionation, 20 phenolic compounds, including eight stilbenoids, were isolated from the roots of Polygonum cuspidatum, and their anti-HIV-1 activities were evaluated. Results showed that compounds 1, 13, 14, and 16 demonstrated fairly strong antiviral activity against HIV-1-induced cytopathic effects in C8166 lymphocytes at non-cytotoxic concentrations, with EC (50) values of 4.37 +/- 1.96 microg/mL, 19.97 +/- 5.09, 14.4 +/- 1.34 microg/mL, and 11.29 +/- 6.26 microg/mL and therapeutic index (TI) values of 8.12, > 10.02, > 13.89, and > 17.71, respectively. Other compounds showed either weak or no effects. Compound 6 also showed weak inhibition (153.42 +/- 19.25 microg/mL); however, it possesses very good water solubility and showed almost no cytotoxicity (> 2000 microg/mL), therefore achieving a fairly good TI (13.04). The activities of the two compounds (3 and 18) from Polygonum multiflorum were also assayed. The relationship between molecular structures and their bioactivities was also discussed.
收起
原文获取