Abstract Background It has long been suggested that human cytomegalovirus (HCMV) might be involved in human oncogenesis. However, whether HCMV was associated with colorectal cancer (CRC) was still ...controversial. Objective To clarify whether HCMV specifically infects the tumorous tissue of CRC. Study design Paired tumor and adjacent non-neoplastic CRC specimens were collected from 163 patients. HCMV DNA was detected and quantified through PCR and quantitative real-time PCR. Virus location was determined by in situ hybridization (ISH) of formalin-fixed paraffin-embedded tissue sections with an HCMV-specific probe. Results By PCR, HCMV DNA was detected in 42.3% (69/163) of the tumor specimens, while only 5.6%(14/163) samples of adjacent non-neoplastic tissue were positive for HCMV ( p < 0.0001). Quantitative real-time PCR in 54 sample pairs revealed significantly higher viral copies in the tumor specimens than the adjacent non-neoplastic tissue specimens ( p < 0.001). By ISH, the nucleic acids of HCMV were detected in the cytoplasm of neoplastic epithelium. No hybridization was detected in the inflammatory infiltrates, submucosa, or other stromal tissues. Conclusions HCMV preferentially infects the tumor epithelium of CRC. How the virus subsists in and interacts with the microenvironment of tumor epithelium of CRC should be studied.
In the present work, gasochromic tungsten oxide (WO3) thin films on glass substrate were fabricated by Pulsed Laser Deposition (PLD) system. Pt was sputtered on the surface of WO3 thin films as a ...catalyst layer for hydrogen gas detection. The gasochromic properties of Pt/WO3 thin films at room temperature were determined by examining their optical transmittance under various H2–N2 mixture gas exposures. The results show that in low H2 atmosphere (0.5%) the room temperature grown Pt/WO3 thin films still exhibited noticeable transmittance change, within the visible light (550–700nm) range. WO3 thin films have been characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). XRD and TEM confirmed that the morphology of the best performance WO3 thin film is amorphous, and SEM investigations revealed that the thin films were composed of nanotextured grains.
A real-time muscle fatigue monitoring system was developed to quantitatively detect the muscle fatigue of subjects during cycling movement, where a fatigue progression measure (FPM) was built-in. ...During the cycling movement, the electromyogram (EMG) signals of the vastus lateralis and gastrocnemius muscles in one leg as well as cycling speed are synchronously measured in a real-time fashion. In addition, the heart rate (HR) and the Borg rating of perceived exertion scale value are recorded per minute. Using the EMG signals, the electrical activity and median frequency (MF) are calculated per cycle. Moreover, the updated FPM, based on the percentage of reduced MF counts during cycling movement, is calculated to measure the onset time and the progressive process of muscle fatigue. To demonstrate the performance of our system, five young healthy subjects were recruited. Each subject was asked to maintain a fixed speed of 60 RPM, as best he/she could, under a constant load during the pedaling. When the speed reached 20 RPM or the HR reached the maximal training HR, the experiment was then terminated immediately. The experimental results show that the proposed system may provide an on-line fatigue monitoring and analysis for the lower extremity muscles during cycling movement.
Patients with diabetes have a relatively high risk of fracture due to osteoporosis. However, the risk of osteoporosis associated with the use of oral hypoglycemic drugs and dipeptidyl peptidase-4 ...inhibitor (DPP-4i) by patients with diabetes is unclear. This study aimed to explore the effect of DPP-4i on the risk of osteoporosis in Taiwanese patients with type 2 diabetes mellitus (T2DM).
This study enrolled 6339 patients on DPP-4i (DPP-4i group) and 25 356 patients without DPP-4i (non-DPP-4i group). They were matched by 1:4 propensity score matching, using confounding variables including sex, age, comorbidities, medication, and index year. Cox proportional hazards analysis was used to compare hospitalization and mortality during an average follow-up period of 7 years.
The mean age of patients in the two groups was 66 years. Men were slightly higher in number (51.79%) than women. At the end of the follow-up period, 113 (0.36%) patients had osteoporosis, of which 15 (0.24%) were in the case group and 98 (0.39%) in the control group. The risk of all-cause osteoporosis was significantly lower in the DPP-4i group than in the non-DPP-4i group (adjusted hazard ratio HR 0.616; 95% confidence interval CI 0.358-0.961; p = 0.011). Kaplan-Meier analysis showed that the preventive effect on osteoporosis was positively correlated with the cumulative dose of DPP-4i (log-rank, p = 0.039) with the class effect.
Compared with not using DPP-4i, the use of DPP-4i in Taiwanese T2DM patients was associated with a lower risk of osteoporosis due to the class effect, and the preventive effect was dose-dependent. However, larger prospective studies are needed to validate this finding and to explore the possible mechanism of the preventive effect of DPP-4i.
We present prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker chromosome (sSMC) derived from chromosome 15 in a pregnancy associated with recurrent Down ...syndrome.
A 33-year-old, gravida 4, para 2, woman underwent amniocentesis at 16 weeks of gestation because of a previous child with Down syndrome and a karyotype of 46,XY,der(14;21)(q10; q10),+21. In this pregnancy, amniocentesis revealed a karyotype of 47,XX,+2112/48,XX,+21,+mar3. The parental karyotypes were normal. The pregnancy was terminated, and a malformed fetus was delivered with characteristic craniofacial appearance of Down syndrome and hypoplastic middle phalanx of the fifth fingers. The placenta had a karyotype of 47,XX,+2137/48,XX,+21,+mar3. The umbilical cord had a karyotype of 47,XX,+2138/48,XX,+21,+mar2. In addition to trisomy 21, array comparative genomic hybridization (aCGH) on the DNA extracted from umbilical cord revealed 40∼50% mosaicism for a 2.604-Mb duplication of 15q25.2–q25.3, or arr 15q25.2q25.3 (83,229,665–85,834,131) × 2.4 GRCh37 (hg19) encompassing 19 Online Mendelian Inheritance in Man (OMIM) genes. Quantitative fluorescent polymerase chain reaction (QF-PCR) using the DNAs extracted from cultured amniocytes and parental bloods revealed maternal origin of the sSMC(15) and the extra chromosome 21.
Conclusion: aCGH is useful for identification of the nature of sSMC, and QF-PCR is useful for determination of the parental origin of the aberrant chromosomes.
Human cytomegalovirus (HCMV) has been increasingly detected in colorectal cancer (CRC), and genetic polymorphisms in HCMV affect its pathogenesis. This study aimed to investigate HCMV genetic ...polymorphisms in CRC and its correlation with the clinical outcomes. We performed PCR and sequencing of a viral immunomodulatory gene, UL144, in clinical isolates and CRC specimens. The nucleotide and amino acid sequences were aligned, and a phylogenetic tree was constructed. The clinical, pathological and survival data were compared among tumours with different UL144 genotypes. HCMV was detected in 49 (47.8 %) of the tumour specimens. Genotype A predominated in 43 samples (22/43; 51.2 %) with successful sequencing, followed by genotype B (13/43; 30.2 %) and genotype C (8/43; 18.6 %). The genotypic distribution was similar to that of the clinical isolates and those reported in other Asian populations. The amino acid sequence of genotype B was the most conserved. For stage II and III CRC patients with HCMV-positive tumours, disease-free survival (DFS) varied among the three major genotypes (P50.0046). The presence of genotype B virus in the tumours was associated with a shorter DFS and independently predicted tumour recurrence in a multivariate Cox proportional hazards model (hazard ratio, 5.79; 95 % confidence interval, 1.30–25.81; P50.021). By reverse transcription PCR, tumour samples with genotype B viruses had the highest rate of UL144 expression. Our results suggest that genetic polymorphisms of HCMV UL144 are associated with clinical outcome in CRC and that HCMV may play an immunomodulatory role in the tumour microenvironment of CRC.
A clinical hallmark of hypertension is impairment of the cardiac vagal baroreflex, which maintains stable blood pressure and heart rate under physiological conditions. There is also evidence that ...oxidative stress in the brain is associated with neurogenic hypertension. We tested the hypothesis that an augmented superoxide level in the nucleus tractus solitarii (NTS), the terminal site of baroreceptor afferents, contributes to the depression of cardiac vagal baroreflex by disrupting the connectivity between the NTS and the nucleus ambiguus (NA), the origin of the vagus nerve, during neurogenic hypertension. An experimental model of neurogenic hypertension that employed intracerebroventricular infusion of angiotensin II in male adult C57BL/6 mice was used. Based on tractographic evaluations using magnetic resonance imaging/diffusion tensor imaging of the medulla oblongata in the brain stem, we found that the connectivity between the NTS and NA was disrupted in neurogenic hypertension, concurrent with impairment of the cardiac vagal baroreflex as detected by radiotelemetry. We further found that the disrupted NTS–NA connectivity was reversible, and was related to oxidative stress induced by augmented levels of NADPH oxidase-generated superoxide in the NTS. We conclude that depression of the cardiac vagal baroreflex induced by oxidative stress in the NTS in the context of neurogenic hypertension may be manifested in the form of dynamic alterations in the connectivity between the NTS and NA.
•A clinical hallmark of hypertension is impairment of the cardiac vagal baroreflex.•We visualized this impairment in a mouse model of neurogenic hypertension by MRI/DTI.•The connectivity between the nucleus tractus solitarii and nucleus ambiguus was disrupted during hypertension.•This disruption was reversibly related to NADPH oxidase-generated superoxide in NTS.•These results offered a new direction for future design of antihypertensive therapy.
Graphene oxide (GO) has been widely used in biological sensing studies because of its excellent physical and chemical properties. In particular, the rich functional groups on the surface of GO can ...effectively enhance the bonding of biomolecules and serve as an efficient sensing substrate. However, when biomolecules are labeled with fluorescence, the GO interface affects the biomolecules by reducing the fluorescence properties and limiting their applications in biosensing. Here, we establish an annealed GO (aGO) substrate through the annealing process, which can effectively increase the bonding amount of a DNA probe because of the accumulation of oxygen atoms on the surface without significantly damaging the nanosheet structure. Furthermore, we prove that the aGO substrate can effectively maintain its fluorescence performance and stability by exposing more graphic domains. Overall, this study successfully verifies that GO’s interface annealing modification can be used as an alternative innovative interface application in biosensing.
Gefitinib is the first-line chemotherapeutic drug for treating non-small cell lung cancer (NSCLC), which comprises nearly 85% of all lung cancer cases worldwide. However, most patients eventually ...develop drug resistance after 12–18months of treatment. Hence, investigating the drug resistance mechanism and resistance-associated biomarkers is necessary. Two lung adenocarcinoma cell lines, PC9 and gefitinib-resistant PC9/Gef, were established for examining resistance mechanisms and identifying potential therapeutic targets. Two-dimensional differential gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry were used for examining global protein expression changes between PC9 and PC9/Gef. The results revealed that 164 identified proteins were associated with the formation of gefitinib resistance in PC9 cells. Additional studies using RNA interference showed that progesterone receptor membrane component 1 and pericentrin proteins have major roles in gefitinib resistance. In conclusion, the proteomic approach enabled identifying of numerous proteins involved in gefitinib resistance. The results provide useful diagnostic markers and therapeutic candidates for treating gefitinib-resistant NSCLC.
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•164 proteins associated with gefitinib resistance were identified through proteomic analysis.•In this study, a lung adenocarcinoma and its gefitinib resistant partner were established.•mPR and PCNT proteins have evidenced to play important roles in gefitinib resistance.
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