2011 Vol. 25, No. 3
Epidemiological and laboratory-based studies have identified infection with one of 15 high-risk human papillo-mavirus (HPV) types as a necessary but not sufficient cause of cervical cancer. The prevalence of genital HPV in-fections is high in young women, but most of the infections regress without interventions. Host genetic variations in genes involved in immune response pathways may be related to HPV clearance, and HPV E6/E7 oncoproteins interacting or downstream genes, both coding and non-coding, may contribute to the outcome of high risk HPV infection and cervical cancer. Of specific interest for this review has been the selection of genetic variants in genes involved in the above-referred pathways with a summary of their applications in association studies. Because the supportive and opposing data have been reported in different populations, well-designed international collabora-tive studies need to be conducted to define the consistency of the associations, paving the way to better define the patients at high risk of developing cervical cancer.
A fundamental goal in cellular signaling is to understand allosteric communication, the process by which sig-nals originating at one site in a protein propagate reliably to affect distant functional sites. The general principles of protein structure that underlie this process remain unknown. Statistical coupling analysis (SCA) is a statistical technique that uses evolutionary data of a protein family to measure correlation between distant functional sites and suggests allosteric communication. In proteins, very distant and small interactions between collections of amino acids provide the communication which can be important for signaling process. In this paper, we present the SCA of protein alignment of the esterase family (pfam ID: PF00756) containing the sequence of antigen 85C secreted by Mycobacterium tuberculosis to identify a subset of interacting residues. Clustering analysis of the pairwise correlation highlighted seven important residue positions in the esterase family alignments. These resi-dues were then mapped on the crystal structure of antigen 85C (PDB ID: 1DQZ). The mapping revealed corre-lation between 3 distant residues (Asp38, Leu123 and Met125) and suggests allosteric communication between them. This information can be used for a new drug against this fatal disease.
MicroRNAs (miRNAs) play an important role in carcinogenesis in various solid cancers including breast can-cer. Down-regulation of microRNA-148a (miR-148a) has been reported in certain cancer types. However, the biological role of miR-148a and its related targets in breast cancer are unknown yet. In this study, we showed that the level of miR-148a was lower in MCF7 cells than that in MCF10A cells. V-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (ERBB3) is a direct target of miR-148a in human breast cancer cells through direct binding of miR-148a to ERBB3 3’-UTR region. Overexpression of miR-148a in MCF7 cells inhibited ERBB3 expression, blocked the downstream pathway activation including activation of AKT, ERK1/2, and p70S6K1, and decreased HIF-1α expression. Furthermore, forced expression of miR-148a attenuated tumor angiogenesis in vivo. Our re-sults identify ERBB3 as a direct target of miR-148a, and provide direct evidence that miR-148a inhibits tumor an-giogenesis through ERBB3 and its downstream signaling molecules. This information would be helpful for target-ing the miR-148a/ERBB3 pathway for breast cancer prevention and treatment in the future.
Toll-like receptor 2 (TLR2) has recently been shown to be up-regulated in patients with non-valvular atrial fi-brillation (AF). The present study was aimed to determine whether the pathogenesis and development of AF is associated with the up-regulation of TLR2. Clinical data and right atrial appendage (RAA) specimens were col-lected from 20 patients with persisten AF (PeAF), 15 patients with paroxysmal AF (PaAF) and 13 patients with no history of AF undergoing valvular replacement. The results showed that gene expression and protein content of TLR2 were increased in both the AF subgroups, compared with the sinus rhythm (SR) group. Between the two AF subgroups, PaAF had a higher TLR2 level than PeAF. However, no difference in interluekin (IL)-6 content was found among the three groups, and no correlation was found between TLR2 and IL-6 in PeAF patients (r = 0.090, P = 0.706), PaAF patients (r = 0.408, P = 0.131) and AF patients (r = -0.301, P = 0.079). Immunohistochemical analysis revealed that TLR2 was distributed in RAAs of AF patients and confirmed the immunoblotting results. In conclusion, we demonstrated that TLR2 was elevated in AF (especially PaAF) patients with valvular heart disease, further implicating inflammation involved in the pathogenesis and development of AF.
The aim of the present study was to compare the effects of colloid and crystalloid preload on cardiac output (CO) and incidence of hypotension in elderly patients under spinal anesthesia (SA). A randomized, double-blinded study was conducted including 47 elderly patients undergoing scheduled total hip replacement (THR), who were randomized to three groups: the control group (C group, n = 15), crystalloid (RS group, n =16) and colloid group (HES group, n = 16). An intravenous preload of 8 mL/kg of either lactated Ringer’s solution in the RS group or 6% hydroxyethyl starch in the HES group was infused within 20 min before SA induction, while no intravenous preload was given in the C group. There was a trend of decrease in CO and systolic blood pressure after SA with time in the C group. In the RS and HES groups, CO increased significantly after fluid preloading as compared with baseline (P < 0.01). Thereafter, CO remained higher than baseline until 30 min after SA in the HES group. The change of systolic blood pressure was similar to CO, but no significant difference from baseline was observed in each group. Hypotension occurred in 3 patients in the C group and one each in the RS and HES group, respec-tively (P = 0.362). Intravascular volume preload with colloid is more effective than crystalloid solution in main-taining CO, which may be improved the hemodynamic stability in elderly patients during SA.
The present study was aimed to investigate the effects of infusion of different fluids combined with control-led hypotension on gastric intramucosal pH (pHi) and postoperative gastrointestinal function in patients undergo-ing hepatocarcinoma surgery. Forty-five patients (ASAⅡ) scheduled for surgical resection of hepatocarcinoma undergoing controlled hypotension were randomly assigned to three groups and received infusion of 20 mL/kg Ringer’s solution (R group), 6% HAES(H group) or 6% Voluven group (W group). Intragastric PgCO2, pHi, he-matocrit and hemoglobin were measured. The significant decrease of pHi and increase of PgCO2 were produced at 1 and 2 h after controlled hypotension in the R group (P < 0.05 or P < 0.01). The time of bowel movement af-ter operation was shorter in the W group than the R group. Meanwhile, we also did not find obvious difference in blood gas indexes among the three groups. The infusion of HAES and Voluven during controlled hypotension could improve gastrointestinal perfusion and accelerate the recovery of postoperative gastrointestinal function.
The aim of the present study was to compare the relationship of morphologically defined non-bulging/herni-ated, bulging and herniated intervertebral lumbar discs with quantitative apparent diffusion coefficient (ADC). Thirty-two healthy volunteers and 28 patients with back pain or sciatica were examined by MRI. All intervertebral lumbar discs from L1 to S1 were classified according to morphological abnormality and degenerated grades. The ADC values of nucleus pulposus (NP) were measured and recorded. The significant differences about mean ADC values of NP were found between non-bulging/herniated discs and bulging discs as well as herniated discs (P < 0.05), whereas there were no significant differences in ADC values between bulging and herniated discs (P > 0.05). Moreover, statistically significant relationship was found in the mean ADC values of NP between "non-bulging/herniated and non-degenerated discs" and "non-bulging/herniated degenerated discs" as well as herniated discs (P < 0.05). Linear regression analysis between ADC value and disc level revealed an inverse correlation (r = -0.18). The ADC map of the NP is a potentially useful tool for the quantitative assessment of componential and molecular alterations accompanied with lumbar disc abnormalities.
Angiogenesis in ischemic tissue is a complex and multi-gene event. In the study, we constructed hypoxic re-sponse elements (HRE) and the Tet-On advanced double-controlled systems and investigated their effects on the expression of hVEGF165 and angiopoietin-1 (Ang-1) genes in rat cardiomyocytes exposed to hypoxia and pharma-cologic induction. We infected neonatal rat cardiomyocytes with recombinant rAAV-rtTA-Rs-M2/rAAV-TRE-Tight-Ang-1 and rAAV-9HRE- hVEGF165. Our results indicated that the viral titer was 1×1012 vg /mL and the viral purity exceeded 98%. hVEGF165 expression was induced by hypoxia, but not by normoxia (P < 0.001). Ang-1 expression was evident under doxycycline induction, but undetectable without doxycycline induction (P < 0.001). Immunofluorescence staining showed that positively stained hVEGF165 and Ang-1 protein appeared only under both hypoxia and doxycycline induction. We demonstrate here that HRE and the recombinant Tet-On advanced double gene-controlled systems sensitively regulate the expression of hVEGF165 and Ang-1 genes in an altered oxygen environment and under pharmacological induction in vitro.
2011, 25(3): 213-219. doi: 10.1016/S1674-8301(11)60028-6
Aldosterone quantification helps evaluate the rennin-angiotensin-aldosterone system. The new bead-based mul-tiplex platform has not been applied in aldosterone detection to achieve simultaneous measurements of multiple hormones. A new sensitive competitive bead immunoassay based on Luminex technology for detecting aldoster-one in small sample volumes was developed using two-antibody coupled beads and biotinylated aldosterone as tracer in combination with an extraction step. The assay was validated in human and mouse samples and exhibited a linear working range from 10 to 1,000 pg/mL. The assay was reproducible and precise with intra-assay coeffi-cient of variations (CVs) from 6.0% to 11.2%, inter-assay CVs from 8.0% to 13.0% and good recovery [(90-110)%] and linearity [(89-107)%]. Excellent correlation was found between this new assay and the reference method (r = 0.96, P < 0.000,1). The successful establishment of this assay provides high possibility for carrying out bead-based multiplex assay measuring aldosterone and other parameters simultaneously in one 50 μL sample so that the efficiency can be improved and precious samples can be saved.
In the study, we sought to retrospectively analyze the effectiveness and safety of surgical repair of thoracoab-dominal aortic aneurysm using the critical artery reattachment technique. Twenty-three consecutive thoracoab-dominal aortic aneurysm patients were treated using the technique of sequential aortic clamping and critical artery reattachment. The entire procedure was technically successful in all patients. One died of renal failure and the overall hospital mortality was 4.35%. The total incidence of complications was 21.74%. At a median follow-up of 33 months, all patients were alive. We found that the application of critical artery reattachment technique in the management of thoracoabdominal aortic aneurysm provides excellent short- and mid-term results in most patients. It could markedly increase the curing rate and reduce the morbidity of postoperative complications including par-aplegia, ischemia of abdominal viscera, and renal failure.
We report the case of a 10-month old girl with a significant past medical history who presented for elective sur-gery with a new-onset fixed, dilated pupil. We briefly review the diagnostic approach to such patients and provide guidelines for managing these patients in the immediate preoperative setting.