2010 Vol. 24, No. 1
Spinal cord injury disrupts the connections between the brain and spinal cord, often resulting in the loss of sensory and motor function below the lesion site. The most important reason for such permanent functional deficits is the failure of injured axons to regenerate after injury. In principle, the functional recovery could be achieved by two forms of axonal regrowth: the regeneration of lesioned axons which will reconnect with their original targets and the sprouting of spared axons that form new circuits and compensate for the lost function. Our recent studies reveal the activity of the mammalian target of rapamycin (mTOR) pathway, a major regulator of new protein synthesis, as a critical determinant of axon regrowth in the adult retinal ganglion neurons. In this review, I summarize current understanding of the cellular and molecular mechanisms that control the intrinsic regenerative ability of mature neurons.
Cardiolipin (CL) is a phospholipid exclusively localized in inner mitochondrial membrane where it is required for oxidative phosphorylation, ATP synthesis, and mitochondrial bioenergetics. The biological functions of CL are thought to depend on its acyl chain composition which is dominated by linoleic acids in metabolically active tissues. This unique feature is not derived from the de novo biosynthesis of CL, rather from a remodeling process that involves in phospholipases and transacylase/acyltransferase. The remodeling process is also believed to be responsible for generation of CL species that causes oxidative stress and mitochondrial dysfunction. CL is highly sensitive to oxidative damages by reactive oxygen species (ROS) due to its high content in polyunsaturated fatty acids and location near the site of ROS production. Consequently, pathological remodeling of CL has been implicated in the etiology of mitochondrial dysfunction commonly associated with diabetes, obesity, heart failure, neurodegeneration, and aging that are characterized by oxidative stress, CL deficiency, and abnormal CL species. This review summarizes recent progresses in molecular, enzymatic, lipidomic, and metabolic studies that support a critical regulatory role of pathological CL remodeling as a missing link between oxidative stress and mitochondrial dysfunction in metabolic diseases and aging.
2010, 24(1): 16-25.
Over the last decade, there has been a flurry of research on adjuvants for vaccines, and several novel adjuvants are now licensed products or in late stage clinical development. The success of adjuvants in enhancing the immune response to antigens has led many researchers to re-focus their vaccine development programs. Although several vaccine candidates have been tested against leishmaniasis, there is yet no effective vaccine against this parasitic disease. Recent research has documented that efforts to develop effective Leishmania vaccine have been limited due to lack of an appropriate adjuvant. In view of this, this review paper outlines some of the adjuvants that have been used in Leishmania vaccine candidates and cites a few of the responses obtained from these studies. The aim of the present review is to consolidate these findings to facilitate the application of these adjuvants in general and experimental vaccinology.
Objective: Nanoparticles are becoming an important method of targeted drug delivery. To evaluate the importance of folate-conjugated human serum albumin (HSA) magnetic nanoparticles (Folate-CDDP/HSA MNP), we prepared drug-loaded Folate-CDDP/HSA MNPs and characterized their features. Methods: First, folate was conjugated with HSA under the effect of a condensing agent, and the conjugating rate was evaluated by a colorimetric method using 2, 4, 6 - trinitrobenzene sulfonic acid. Second, under N2 gas, Fe3O4 magnetic nanomaterials were prepared and characterized by using transmission electron microscopy (TEM), SEM-EDS and X-ray diffraction (XRD). Finally, Folate-CDDP/HSA MNP was prepared by using a solvent evaporation technique. TEM was used to observe particle morphology. The particle size and distribution of the prepared complexes were determined by a Laser particle size analyzer. Drug loading volume and drug release were investigated by a high performance liquid chromatography method (HPLC) in vitro. Results: We successfully prepared folate-conjugated HSA and its conjugating rate was 27.26 μg/mg. Under TEM, Fe3O4 magnetic nanoparticles were highly electron density and had an even size distribution in the range of 10-20 nm. It was confirmed by SEM-EDS and XRD that Fe3O4 magnetic nanoparticles had been successfully prepared. Under TEM, drug-loaded magnetic nanoparticles were observed, which had a round shape, similar uniform size and smooth surface. Their average size was 79 nm which was determined by laser scattering, and they exhibited magnetic responsiveness. Encapsulation efficiency was 89.75% and effective drug loading was calculated to be 15.25%. The release results in vitro showed that the half release time (t1/2) of cisplatin in cisplatin Solution and Folate-CDDP/HSA MNP was 65 min and 24 h respectively, which indicated that microspheres had an obvious effect of sustained-release. Conclusion: Folate-CDDP/HSA MNPs were prepared successfully. The preparation process and related characteristics data provided a foundation for further study, including the mechanism of the nanoparticles distribution in vivo and their intake by tumor cells.
Small non-coding RNAs with important regulatory roles are not confined to eukaryotes. Recent work has uncovered a growing number of bacterial small RNAs (sRNAs), some of which have been shown to regulate critical cellular processes. Computational approaches, in combination with molecular experiments, have played an important role in the identification of these sRNAs. At present, there is no information on the presence of small non-coding RNAs and their genes in the Agrobacterium tumefaciens genome. To identify potential sRNAs in this important bacterium, deep sequencing of the short RNA populations isolated from Agrobacterium tumefaciens C58 was carried out. From a data set of more than 10,000 short sequences, 16 candidate sRNAs have been tentatively identified based on computational analysis. All of these candidates can form stem-loop structures by RNA folding predictions and the majority of the secondary structures are rich in GC base pairs. Some are followed by a short stretch of U residues, indicative of a rho-independent transcription terminator, whereas some of the short RNAs are found in the stem region of the hairpin, indicative of eukaryotic-like sRNAs. Experimental strategies will need to be used to verify these candidates. The study of an expanded list of candidate sRNAs in Agrobacterium will allow a more complete understanding of the range of roles played by regulatory RNAs in prokaryotes.
Objective: Recent studies have shown that the local expression of soluble interleukin (IL) -1 receptor type Ⅱ (sIL-1 RⅡ) in endometrial tissue of women with endometriosis is decreased, and the depression of IL-1 RⅡ was more significant in infertile women than that in fertile women with endometriosis. In this research, we investigated the remedial effect of sIL-1-RⅡ administration on endometriosis in the nude mouse model. Methods: Nineteen nude model mice with endometriosis were randomly divided into three groups: group A was treated by intraperitoneal administration with only sIL-1 RⅡ for two weeks, group B was similarly treated with only IL-1, and group C (control) was administered saline . After 2 weeks, the size of the ectopic endometrial lesions was calculated, and the expression of vascular endothelial growth factor (VEGF) and B-cell lymphoma leukemia-2 (Bcl-2) were detected by immunohistochemistry. The IL-8 and VEGF levels in the peritoneal fluid (PF) and serum were also measured by enzyme-linked immunosorbent assay (ELISA). Results: The mean size of ectopic endometrial lesion did not differ between the three groups (P > 0.05). Compared with the control, the expression of VEGF and Bcl-2 was significantly lower in group A, and higher in group B. In the three groups, the levels of IL-8 in the PF and serum were highest in group A, and lowest in group B. Conclusion: sIL-1 RⅡ may suppresse hyperplasia of ectopic endometriosis, perhaps by reducing the expression of certain cytokines, such as VEGF, IL-8, and Bcl-2, which could provide a new clinical strategy for the treatment of endometriosis.
Objective: Colorectal cancer is one of the major contributors to cancer death worldwide. Lack of reliable colorectal cancer markers has hampered the management of these cancer patients. Our main purpose was to study the correlation between histopathological variables of colorectal adenocarcinomas and identify histopathological markers that are of prognostic value in patients with colorectal cancer. Methods: In the present study, we examined the expression of carcinoembryonic antigen (CEA), p53, Ki-67 and glutathion Stransferase (GST) -π by using immunohistochemical staining methods in 126 colorectal carcinoma patients and evaluated the lymph node metastasis status in these patients by histopathological examination. Results: The positive rates of CEA, p53, Ki-67 and GST-π expression in the colorectal cancer tissue specimens examined were 95.23%, 55.56%, 53.38% and 82.30%, respectively. Expression of p53 and Ki-67 was significantly correlated with the Dukes stages of the tumor, with higher levels of these proteins in Dukes’C and D tumors than those in Dukes’ A and B tumors. Furthermore, the expression of p53, GST-π and Ki-67 correlated with prognosis of patients with colorectal cancer. Additionally, the expression of p53 in colorectal cancer was closely related to the expression of Ki-67 and the expression of GST-π was directly correlated with that of p53. Conclusion: The expression of CEA, p53, Ki-67 and GST-π was correlated with various clinical features of patients with colorectal cancer. The combined use of these histopathological markers appeared to be a promising tool in predicting the prognosis of patients with this type of cancer.
Objective: To construct a lentiviral vector expressing HIV-1 Tat and identify its expression in 293T cells. Methods: The gene fragment of HIV-1 Tat101 was subcloned to lentiviral transfer vector pHAGE-CMV-MCS-IZsGreen, which was named pHAGE-Tat. Then the constructed pHAGE-Tat was used to co-transfect the packing 293T cells, together with the packaging plasmids pMD2.G and psPAX2. The packaged viral particles designated LV-Tat were used to infect the 293T cells and the viral titer was calculated. The expression of HIV-1 Tat in 293T cells was confirmed using RT-PCR and western blot. Results: The recombinant lentiviral vector was successfully constructed and could express HIV-1 Tat in 293T cells. The virus titer was 5.73×106 ifu/ml. Conclusion: The successfully constructed recombinant lentiviral vector makes a strong foundation for further exploring the possible role of HIV-1 Tat in the development of prostate cancer.
Objective：A major problem in the chemotherapy of colon caner may be due to those cells that are in residence in the G0 phase where they are less vulnerable to conventional therapy. To overcome this phenomenon, we attempted to recruit the reentry of these cells into the cell cycle via a signaling pathway that manipulates tumor growth. Methods: Epidermal growth factor (EGF) was used to stimulate colon cancer caco-2 cells. FACS analysis and proliferating cell nuclear antigen (PCNA) staining were used to estimate the cell cycle transition and cell proliferation activated by EGF, and a MTT assay was used to evaluate the synergistic effect of EGF and chemotherapy. Results: The percentage of caco-2 cells in the G0/G1 phase was significantly reduced by nearly 20% and the percentages in the S and G2/M phases were increased by EGF. The combined use of EGF and 5-fluorouracil (5-FU) enhanced the caco-2 cell chemosensitivity to 5-FU, reaching a maximum of an approximately threefold greater sensitivity than to 5-FU alone as judged by the 50% inhibiting concentration (IC50). Conclusion: Our study demonstrated that stimulation by EGF enhanced the chemosensitivity of caco-2 cells to 5-FU, which may be a novel therapeutic protocol in colon cancer.
Objective: To evaluate the changes in Tp-e interval (an interval from the peak to the end of the T wave), QT interval and Tp-e/QT ratio of the body surface ECG in patients with left ventricular hypertrophy (LVH). Methods: The Tp-e interval and QT interval were measured on body surface ECGs in 42 patients without either hypertension or LVH (control group), 41 patients having hypertension but not LVH (non-LVH group), and 38 patients with both hypertension and LVH (LVH group). Results: The mean corrected QT (QTc) interval, and mean corrected Tp-e[T(p-e)c] interval were significantly longer in the LVH group (0.430±0.021s vs. 0.409±0.019s, p < 0.01; 0.098±0.013s vs. 0.088±0.011s, respectively) than those in the control group. The Tp-e/QT ratio was also amplified in LVH group (0.232±0.028 vs.0.218±0.027) (p < 0.05). Conclusion: LVH increased the QT interval, Tp-e interval and Tp-e/QT ratio of the body surface ECG.
Objective: To summarize the clinical experiences of 21 patients treated with tricuspid valve replacement (TVR) and investigate the surgical indications and methods. Methods: Data from 21 patients who underwent TVR from December 2002 to March 2009 were retrospectively collected and analyzed. The mean age was 48.86±15.37 years (range: 20-72 years). The underlying disease of the patients was classified as rheumatic (n = 10), congenital (n = 8), endocarditis (n = 2) or chest trauma (n = 1). Previous cardiac surgery had been performed in 12 patients (57.14%). Results: In-hospital death occurred in two patients (9.52%). Postoperative morbidities included cardiac failure (n = 2), bleeding related re-operation (n = 1), and plural effusion (n = 2). Conclusion: The early outcomes of TVR were acceptable. At the present time TVR can be performed through optimal perioperative management.
A 69-year-old woman with angina had a lesion in the left lower lobe on chest film. Angiography revealed coronary artery disease in three vessels. Combined off pump coronary artery bypass grafting (CABG) and left lower lobectomy were performed through median sternotomy. This approach avoids complications due to staged operations and cardiopulmonary bypass (CPB). This report shows that simultaneous off pump CABG and pulmonary operations can be performed safely in patients with coronary artery disease (CAD) associated with lung cancer.
A 41-year-old woman presented with a pruritic rash on the face that was of 3 months duration. During that time, it had been successively misdiagnosed as psoriasis vulgaris, systemic lupus erythematosus, facial dermatitis at other hospitals, and had been treated with agents that included acitretin and prednisone. Finally, fungi were found in the lesions by optical microscopy, and the fungal culture was positive for Microsporum gypseum, and was diagnosed as a Microsporum gypseum infection. The lesions eventually cleared completely after 8 weeks of antifungal treatment.