Zhou R.-H.,Guangxi Medical University
Journal of Acquired Immune Deficiency Syndromes | Year: 2017
BACKGROUND:: Human semen contains a factor that can enhance HIV infection up to 10^5-fold in cultures. This factor is termed SEVI (Semen-derived Enhancer of Virus Infection), which is composed of proteolytic fragments (PAP248-286) from prostatic acid phosphatase (PAP) in semen. Here, we examined whether macaque SEVI can facilitate simian immunodeficiency virus (SIV) or chimeric simian/human immunodeficiency virus (SHIV) infection. We also studied the effect of EGCG on macaque SEVI-mediated SIV or SHIV enhancement. METHODS:: SIV or SHIV was mixed with different concentrations of macaque SEVI in the presence or absence of epigallocatechin gallate (EGCG). The mixture was added to cultures of TZM-bl cells or macaque PBMC. The effect of EGCG on macaque SEVI was measured by Congo-red staining assay, thioflavin T (ThT) fluorescence assay and visualized by a transmission electron microscope. RESULTS:: We identified that there is one amino acid difference at the site of 277 between human PAP248-286 and macaque PAP248-286. Macaque SEVI significantly enhanced SIV or SHIV infection of TZM-bl cells and macaque PBMC. EGCG could block macaque SEVI-mediated enhancement of SIV or SHIV infection. Mechanistically, EGCG could degrade the formation of macaque SEVI amyloid fibrils that facilitates HIV attachment to the target cells. CONCLUSIONS:: The finding that macaque SEVI could enhance SIV or SHIV infection indicates the possibility to use the macaque SEVI in vivo studies with the macaque models. In addition, future studies are necessary to examine whether EGCG can be used as an effective microbicide for preventing SIV or SHIV mucosal transmission. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
News Article | August 25, 2016
Multidrug resistance (MDR) is the mechanism by which many cancers develop resistance to chemotherapy drugs, resulting in minimal cell death and the expansion of drug-resistant tumors. To address the problem of resistance, researchers have developed nanoparticles that simultaneously deliver chemotherapy drugs to tumors and inhibit the MDR proteins that pump the therapeutic drugs out of the cell. The process is known as chemosensitization, as blocking this resistance renders the tumor highly sensitive to the cancer-killing chemotherapy. MDR is a major factor in the failure of many chemotherapy drugs. The problem affects the treatment of a wide range of blood cancers and solid tumors, including breast, ovarian, lung, and colon cancers. Researchers at the National Institute of Biomedical Imaging and Bioengineering (NIBIB), a part of the National Institutes of Health (NIH), are engineering multi-component nanoparticles that significantly enhance the killing of cancer cells. The results of their experiments are reported in recent articles in Scientific Reports and Applied Materials & Interfaces. The work is led by senior author Xiaoyuan (Shawn) Chen, Ph.D., Senior Investigator, Laboratory of Molecular Imaging and Nanomedicine, NIBIB. His collaborators include scientists and engineers in China at Southeast University, Shenzhen University, Guangxi Medical University, and Shanghai Jiao Tong University, in addition to chemical engineers at the University of Leeds, United Kingdom. Says Chen about his substantial network of collaborators, “success in this medically important endeavor has required a team with a wide range of expertise to engineer nanoparticles that survive the journey to the tumor site, enter the tumor, and successfully perform the multiple functions for chemosensitization.” Targeting Multidrug-resistant Breast Cancer The two publications report on the engineering of two separate nanoparticles that test different strategies for achieving chemosensitization of cancer cells. The first targets MDR breast cancer. The engineered round nanoparticle is made of several layers. The center of the particle is loaded with the anti-cancer drug doxorubicin. The drug is surrounded by a water-repelling (hydrophobic) capsule to protect it from the watery environment when the particle is injected into the circulatory system of an experimental animal or individual with cancer. The particle has several outer layers with different properties. One of the outermost components, a molecule called PEG, is hydrophilic (mixes with water) and helps the particle move through the bloodstream until it encounters the breast tumor cells. Another component on the surface of the particle, biotin, functions to bind specifically to the cancer cells and helps the drug-carrying nanoparticle to enter the cell. Once inside the breast cancer cell, a fourth component called curcumin, which is intertwined with the doxorubicin center, is released along with the doxorubicin. The curcumin is the component that blocks the cell machinery that would pump the doxorubicin out of the cell. Without the ability to pump out the medicine, the cell is exposed to very high concentration of doxorubicin, which kills the breast cancer cells. Experiments in mice demonstrated that the multi-component nanoparticles were effective at targeting breast tumor cells—accumulating at much higher concentrations in the cancer cells than in the other mouse tissues. Histology showed that the treated mice had a great reduction in cancer cell density in the tumor tissue compared with mice given saline or doxorubicin alone (not integrated into a nanoparticle). Complete analysis of the treated mice confirmed that the nanoparticle efficiently accumulated at the tumor site and achieved optimal tumor killing in the mouse breast cancer model. Changing Nanoparticle Components Tests Alternate Anti-cancer Strategies In the work published in Applied Materials & Interfaces, Chen and his colleagues describe the engineering of another nanoparticle that uses a different approach to the problem of MDR. This second nanoparticle is similar to the first in that it contains the centrally encapsulated doxorubicin surrounded by an outer hydrophilic surface layer that allows efficient transport through the bloodstream. However, this particle uses the gas nitric oxide (NO), which is known to block the system that pumps doxorubicin out of the cell. In addition, the NO is released from a compound called BNN6, which is activated by ultraviolet (UV) light. Thus, this nanoparticle is designed to be administered in the bloodstream and then activated with UV light when it reaches its cancer target. In experiments in cell culture, when hit with UV light the nanoparticles burst -- releasing the cell-killing doxorubicin and causing BNN6 to release the NO gas. The combination successfully inhibited the MDR machinery, resulting in chemosensitization and efficient cancer-cell killing. Based on the successful testing of this nanoparticle in cultured cells, the group expects it to perform well when tested in experiments in mice. Smart Nanomedicines vs Multidrug Resistance Chemotherapy is the most common treatment for cancer. Unfortunately, these drugs often cause minimal damage to tumors, because of MDR, and this can result in the expansion of populations of MDR tumors. Also, most chemotherapy drugs have very narrow therapeutic windows, frequently showing toxicity to healthy tissues and organs even at doses lower than required for a therapeutic effect. Therefore, there is an urgent need to devise ways to achieve high doses in tumor cells while eliminating harm to healthy tissue. Chen concludes, “The mechanism of MDR is interesting scientifically, but also incredibly important medically. That is why we are using our bioengineering skills to develop strategies to optimize the effect of these drugs on the cancer while reducing the toxicity to the surrounding tissues, which is both a major impediment to successful treatment as well as extremely taxing for cancer patients.” The work was funded by support from the Intramural Research Program, NIBIB. Funding from China was provided by The National Key Program for Developing Basic Research, the National Science Foundation, the Shenzhen Basic Research Program, the China Scholarship Council, and the Instrumental Analysis Center of Shanghai Jiao Ton University. Additional funds were provided by the European Union.
Zhou T.-B.,Guangxi Medical University
Journal of Receptors and Signal Transduction | Year: 2012
PAX2, a nuclear transcription factor in renal development, is strongly expressed during kidney development and plays an important role in kidney development, differentiation, and renal cell proliferation. PAX2 is expressed in epithelial cells of fetal kidneys and its expression is up-regulated in certain pathologic conditions. However, the transcription activation of PAX2 and its signaling pathways are complicated. Recent discoveries find that the PAX2 gene is pivotal in kidney development and it is implicated in the pathogenesis of renal interstitial fibrosis (RIF) and glomerulosclerosis (GS). Here, I comprehensively reviewed the signal transduction pathways of PAX2 and its role in the pathogenesis of RIF and GS. © 2012 Informa Healthcare USA, Inc.
Aung Naing K.,Guangxi Medical University
The Cochrane database of systematic reviews | Year: 2013
Primary percutaneous coronary intervention (PPCI) is the preferred treatment for ST segment elevation myocardial infarction. Although there is restoration of coronary flow after PPCI, impaired myocardial perfusion (known as no-reflow) is frequently observed, and is related to poor clinical outcomes. In order to overcome this phenomenon, drugs have been tried as adjunctive treatments to PPCI. Among them, verapamil and adenosine are two of the most promising drugs. There are no systematic reviews of these two drugs in people with acute myocardial infarction (AMI) undergoing PPCI. To study the impact of adenosine and verapamil on people with AMI who are undergoing PPCI. We searched the following databases in February 2012: the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library, MEDLINE, EMBASE, Web of Science and BIOSIS, China National Knowledge Infrastructure, Clinical Trials registers (Clinical Trials.gov, Current Controlled Trials, Australian & New Zealand Clinical Trials Registry, the WHO International Clinical Trials Registry Platform). We also handsearched the American Journal of Cardiology. We selected randomised controlled trials (RCTs) where adenosine or verapamil was the primary intervention. Participants were individuals diagnosed with AMI who were undergoing PPCI. Two review authors collected studies and extracted data. Where necessary, we contacted the trial authors to obtain the relevant information. We calculated risk ratios (RRs), P values, and 95% confidence intervals (CIs) of dichotomous data. We included 10 RCTs involving 939 participants in our review. Nine RCTs were associated with adenosine and one with verapamil. We considered the overall risk of bias of included studies to be moderate. There was no evidence that adenosine reduced short-term all-cause mortality (RR 0.61, 95% CI 0.23 to 1.61, P = 0.32), long-term all-cause mortality (RR 1.20, 95% CI 0.27 to 5.22, P = 0.81), short-term non-fatal myocardial infarction (RR 1.38, 95% 0.28 to 6.96, P = 0.69) or the incidence of angiographic no-reflow (TIMI flow grade < 3 after PPCI: RR 0.72, 95% CI 0.49 to 1.07, P = 0.11, and myocardial blush grade (MBG) 0 to 1 after PPCI: RR 0.96, 95% CI 0.76 to 1.22, P=0.75). But the incidence of adverse events with adenosine, such as bradycardia (RR 6.57, 95% CI 2.94 to 14.67, P<0.00001), hypotension (RR 11.43, 95% CI 2.75 to 47.57, P=0.0008) and atrioventricular (AV) block (RR 6.67, 95% CI 1.52 to 29.21, P=0.01) was significantly increased.Meta-analysis of verapamil as treatment for no-reflow during PPCI was not calculated due to lack of data. We found no evidence that adenosine and verapamil as treatments for no-reflow during PPCI can reduce all-cause mortality, non-fatal myocardial infarction or the incidence of angiographic no-reflow (TIMI flow grade < 3 and MBG 0 to1), but there was some evidence of increased adverse events. Further clinical research into adenosine and verapamil is needed because of the limited numbers of included trials and participants.
Li G.F.,Guangxi Medical University
Genetics and molecular research : GMR | Year: 2012
Breast cancer is a common cancer in women, with a highly variable course, from inoffensive to lethal. To find a more effective strategy for its treatment, sodium valproate has been tested as an anti-cancer drug; it is the only clinically available histone deacetylase inhibitor. However, data about the effects of sodium valproate on breast cancer are insufficient in both animals and humans; studies have yielded conflicting conclusions. In particular, little is known about the association between expression of the metastasis suppressor Nm23H1 gene and breast cancer. We hypothesized that sodium valproate regulates NM23H1 expression, and affects migration and/or invasion. We found that sodium valproate at concentrations of 0.8-3.2 mM inhibits migration and modulates Nm23H1 gene expression in a concentration-dependent manner. Confluent MDA-MB-231 cells were scratched by a micropipette tip after VPA treatment for 24 h; 24 h later, the scratch was almostly closed in the 0 mM VPA-treated cells, while the 3.2 mM VPA-treated cells migrated the slowest. The cell migration ratio exposed to 0.8, 1.6 and 3.2 mM VPA was about 66.67, 30.67 and 26.67% (P < 0.05). We also found evidence that sodium valproate upregulates NM23H1 expression, which is a clue to its anti-cancer mode of action. The NM23H1 gene expression was relative fold increased determined by Western blotting at 3.2 mM VPA. Collectively, these observations indicate that sodium valproate has potential for use in breast cancer treatment.
Li P.,Guangxi Medical University |
Qin C.,Guangxi Medical University
Gene | Year: 2014
Associations between 5,10-methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and ischemic stroke have been reported (Ariyaratnam et al., 2007; Banerjee et al., 2007; Casas et al., 2004), but the results of these studies are inconsistent. To investigate the possible associations between the MTHFR gene polymorphism and ischemic stroke, we performed a meta-analysis. Nineteen case-control studies associated with MTHFR gene C667T involving 2223 cases and 2936 controls were included. Heterogeneity among studies was evaluated with I2 and Egger's test and an inverted funnel plot was used to assess publication bias. Odds ratio (OR) was observed to identify the associations. Statistically significant association with ischemic stroke was identified for allele T polymorphism of MTHFR [fixed-effects OR=1.28, 95% confidence interval (95% CI): 1.17-1.40, P<0.00001] and marginally significant association was detected with genotype CT of MTHFR (fixed-effects OR=1.13, 95% CI: 1.01-127, P=0.04) and genotype TT of MTHFR (fixed-effects OR=1.43, 95% CI: 1.20-1.70, P<0.001). The results suggested that the MTHFR C667T genetic polymorphism was significantly associated with increased risk of ischemic stroke. © 2013.
Zhou T.-B.,Guangxi Medical University
Journal of Receptors and Signal Transduction | Year: 2013
The roles of apolipoprotein E (apoE) in regulating plasma lipids and lipoproteins levels have been investigated for over several decades. However, in different tissues/cells, the role of apoE was different, such as that it was a risk factor for cancer, but some reports stated that apoE was a protective factor for renal diseases. At the moment, most of the studies find that apoE not only acts as a ligand for metabolism of lipids, but also plays as a factor to regulate lots of signaling pathways. There was rare review to sum up the signaling pathways for apoE, and there was also rare review to widely review the gene expression of apoE in glomerulus diseases. This review was performed to provide a relatively complete signaling pathways flowchart for apoE to the investigators who were interested in the roles of apoE in the pathogenesis of glomerulus diseases. In the past decades, some studies were also performed to explore the association of apoE gene expression with the risk of glomerulus diseases. However, the role of apoE in the pathogenesis of glomerulus diseases was controversial. Here, the signal transduction pathways of apoE and its role of gene expression in the pathogenesis of glomerulus diseases were reviewed. © 2013 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
Xiao Y.,Guangxi Medical University
Cochrane database of systematic reviews (Online) | Year: 2012
Inspiratory muscle weakness has been observed in patients with stroke. Inspiratory muscle training is an intervention that has shown possible effects for functional recovery of patients with stroke. To investigate the effect and safety of inspiratory muscle training for improving activities of daily living, respiratory muscle function, quality of life and cardiorespiratory fitness after stroke. We searched the Cochrane Stroke Group's Trials Register (August 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, October Issue 4), MEDLINE (1948 to October 2011), EMBASE (1974 to October 2011), CINAHL (1982 to October 2011), AMED (1985 to October 2011), PEDro (October 2011) and four Chinese databases. In an effort to identify further published, unpublished and ongoing trials, we searched ongoing trials registers and conference proceedings, checked reference lists, and contacted authors of relevant studies and training devices manufactures. There were no language restrictions. Randomised controlled trials (RCTs) comparing inspiratory muscle training with no intervention, sham inspiratory muscle training or other cardiorespiratory training for patients with stroke were eligible. Two review authors independently assessed trial quality and extracted data. The primary outcomes were activities of daily living and respiratory muscle strength; the secondary outcomes were quality of life, cardiorespiratory fitness and adverse effects. We included two trials involving a total of 66 patients in this review. Pooling analyses of data was not possible due to considerable heterogeneity between the trials and a lack of data in both trials. One study found a significant increase in respiratory muscle strength favouring inspiratory muscle training over sham inspiratory muscle training, but there was no significant difference between groups on quality of life. The other study showed that patients receiving inspiratory muscle training were more likely to improve their activities of daily living, quality of life and cardiorespiratory fitness than those patients who received no intervention. However, the main results were not compared directly with breathing retraining. Furthermore, neither of the trials assessed the safety and tolerance of inspiratory muscle training. There is insufficient evidence to support inspiratory muscle training as an effective treatment to improve function after stroke, and no evidence relating to the safety of inspiratory muscle training. Further well-designed RCTs are required.
Zhao J.M.,Guangxi Medical University
Cochrane database of systematic reviews (Online) | Year: 2012
Total hip replacement (THR) is an effective treatment for reducing pain and improving function and quality of life in patients with hip disorders. While this operation is very successful, deep vein thrombosis (DVT) and pulmonary embolism (PE) are significant complications after THR. Different types of intermittent pneumatic compression (IPC) devices have been used for thrombosis prophylaxis in patients following THR. Available devices differ in compression garments, location of air bladders, patterns of pump pressure cycles, compression profiles, cycle length, duration of inflation time and deflation time, or cycling mode such as automatic or constant cycling devices. Despite the widely accepted use of IPC for the treatment of arterial and venous diseases, the relative effectiveness of different types of IPC systems as prophylaxis against thrombosis after THR is still unclear. To assess the comparative effectiveness and safety of different IPC devices with respect to the prevention of venous thromboembolism in patients after THR. The Cochrane Peripheral Vascular Diseases Group Trials Search Coordinator searched the Specialised Register (May 2012), CENTRAL (2012, Issue 4), MEDLINE (April Week 3 2012) and EMBASE (Week 17 2012). Clinical trial databases were searched for details of ongoing and unpublished studies. Reference lists of obtained articles were also screened. There were no limits imposed on language or publication status. Randomized and quasi-randomized controlled studies were eligible for inclusion. Two review authors independently selected trials, assessed trials for eligibility and methodological quality, and extracted data. Disagreement was resolved by discussion or, if necessary, referred to a third review author. Only one quasi-randomized controlled study with 121 study participants comparing two types of IPC devices met the inclusion criteria. The authors found no cases of symptomatic DVT or PE in either the calf-thigh compression group or the plantar compression group during the first three weeks after the THR. The calf-thigh pneumatic compression was more effective than plantar compression for reducing thigh swelling during the early postoperative stage. The strength of the evidence in this review is weak as only one trial was included and it was classified as having a high risk of bias. There is a lack of evidence from randomized controlled trials to make an informed choice of IPC device for preventing venous thromboembolism (VTE) following total hip replacement. More research is urgently required, ideally a multicenter, properly designed RCT including a sufficient number of participants. Clinically relevant outcomes such as mortality, imaging-diagnosed asymptomatic VTE and major complications must be considered.
Wang R.S.,Guangxi Medical University
PloS one | Year: 2013
Observational studies suggest an association between tooth loss and risk of head and neck cancer. However, whether tooth loss is an independent risk factor for head and neck cancer still remains controversial. The aim of this study is to assess the association between tooth loss and head and neck cancer risk. Eligible studies were searched in PubMed and Embase databases from their inception to March 2013. A random-effects model or fixed-effects model was used to calculate the overall combined risk estimates. Eight case-control studies and one cross-sectional study involving 5,204 patients and 5,518 controls were included in the meta-analysis. The overall combined odds ratio for tooth loss and head and neck cancer was 2.00 (95% confidence interval, 1.28-3.14). Similar results yielded both in the moderate and severe tooth loss group. Sensitivity analysis based on various exclusion criteria maintained this significance with respect to head and neck cancer individually. Little evidence of publication bias was observed. This meta-analysis suggests that tooth loss is associated with increased risk of head and neck cancer. This increase is probably independent of conventional head and neck cancer risk factors.