Despite a general repression of translation under hypoxia, cells selectively upregulate a set of hypoxia-inducible genes. Results from deep sequencing revealed that Let-7 and miR-103/107 are hypoxia-responsive microRNAs (HRMs) that are strongly induced in vascular endothelial cells. In silico bioinformatics and in vitro validation showed that these HRMs are induced by HIF1α and target argonaute 1 (AGO1), which anchors the microRNA-induced silencing complex (miRISC). HRM targeting of AGO1 resulted in the translational desuppression of VEGF mRNA. Inhibition of HRM or overexpression of AGO1 without the 3′ untranslated region decreased hypoxia-induced angiogenesis. Conversely, AGO1 knockdown increased angiogenesis under normoxia in vivo. In addition, data from tumor xenografts and human cancer specimens indicate that AGO1-mediated translational desuppression of VEGF may be associated with tumor angiogenesis and poor prognosis. These findings provide evidence for an angiogenic pathway involving HRMs that target AGO1 and suggest that this pathway may be a suitable target for anti- or proangiogenesis strategies.
Aims: The role of endothelium-derived contracting factors (EDCFs) in regulating renovascular function is yet to be elucidated in renovascular hypertension (RH). The current study investigated whether oxidative stress-dependent cyclooxygenase (COX)-2-derived prostaglandin F2α (PGF2α) impairs endothelial function in renal arteries of renovascular hypertensive rats (RHR). Results: Renal hypertension was induced in rats by renal artery stenosis of both kidneys using the 2-kidney 2-clip model. Acute treatment with reactive oxygen species (ROS) scavengers, COX-2 inhibitors, and thromboxane-prostanoid receptor antagonists, but not COX-1 inhibitors, improved endothelium-dependent relaxations and eliminated endothelium-dependent contractions in RHR renal arteries. Five weeks of treatment with celecoxib or tempol reduced blood pressure, increased renal blood flow, and restored endothelial function in RHRs. Increased ROS production in RHR arteries was inhibited by ROS scavengers, but unaffected by COX-2 inhibitors; whereas increased PGF2α release was reduced by both ROS scavengers and COX-2 inhibitors. ROS also induced COX-2-dependent contraction in RHR renal arteries, which was accompanied by the release of COX-2-derived PGF2α. Further, chronic tempol treatment reduced COX-2 and BMP4 upregulation, p38MAPK phosphorylation, and the nitrotyrosine level in RHR renal arteries. Conclusion: These findings demonstrate the functional importance of oxidative stress, which serves as an initiator of increased COX-2 activity, and that COX-2-derived PGF2α plays an important role in mediating endothelial dysfunction in RH. Innovation: The current study, thus, suggests that drugs targeting oxidative stress-dependent COX-2-derived PGF2α may be useful in the prevention and management of RH. Antioxid. Redox Signal. 16, 363–373.
Background: Evidence suggesting that persistent environmental pollutants may be reproductive toxicants underscores the need for prospective studies of couples for whom exposures are measured.
Objectives: We examined the relationship between selected persistent pollutants and couple fecundity as measured by time to pregnancy.
Methods: A cohort of 501 couples who discontinued contraception to become pregnant was prospectively followed for 12 months of trying to conceive or until a human chorionic gonadotrophin (hCG) test confirmed pregnancy. Couples completed daily journals on lifestyle and provided biospecimens for the quantification of 9 organochlorine pesticides, 1 polybrominated biphenyl, 10 polybrominated diphenyl ethers, 36 polychlorinated biphenyls (PCBs), and 7 perfluorochemicals (PFCs) in serum. Using Cox models for discrete time, we estimated fecundability odds ratios (FORs) and 95% CIs separately for each partner’s concentrations adjusting for age, body mass index, serum cotinine, serum lipids (except for PFCs), and study site (Michigan or Texas); sensitivity models were further adjusted for left truncation or time off of contraception (≤ 2 months) before enrollment.
Results: The adjusted reduction in fecundability associated with standard deviation increases in log-transformed serum concentrations ranged between 18% and 21% for PCB congeners 118, 167, 209, and perfluorooctane sulfonamide in females; and between 17% and 29% for p,p´-DDE and PCB congeners 138, 156, 157, 167, 170, 172, and 209 in males. The strongest associations were observed for PCB 167 (FOR 0.79; 95% CI: 0.64, 0.97) in females and PCB 138 (FOR = 0.71; 95% CI: 0.52, 0.98) in males.
Conclusions: In this couple-based prospective cohort study with preconception enrollment and quantification of exposures in both female and male partners, we observed that a subset of persistent environmental chemicals were associated with reduced fecundity.
conception; cotinine; fecundity; organochlorine pesticides; polybrominated diphenyl ethers; polychlorinated biphenyls; perfluorochemicals; time to pregnancy
High-dimensional biomarker data are often collected in epidemiological studies when assessing the association between biomarkers and human disease is of interest. We develop a latent class modeling approach for joint analysis of high-dimensional semicontinuous biomarker data and a binary disease outcome. To model the relationship between complex biomarker expression patterns and disease risk, we use latent risk classes to link the 2 modeling components. We characterize complex biomarker-specific differences through biomarker-specific random effects, so that different biomarkers can have different baseline (low-risk) values as well as different between-class differences. The proposed approach also accommodates data features that are common in environmental toxicology and other biomarker exposure data, including a large number of biomarkers, numerous zero values, and complex mean–variance relationship in the biomarkers levels. A Monte Carlo EM (MCEM) algorithm is proposed for parameter estimation. Both the MCEM algorithm and model selection procedures are shown to work well in simulations and applications. In applying the proposed approach to an epidemiological study that examined the relationship between environmental polychlorinated biphenyl (PCB) exposure and the risk of endometriosis, we identified a highly significant overall effect of PCB concentrations on the risk of endometriosis.
Categorical data; Chemical exposure biomarkers; Latent variables; Monte Carlo EM algorithm; Random effects
In response to ionizing irradiation and certain chemotherapeutic agents, dying tumor cells elicit a potent anticancer immune response. However, the potential effect of wogonin (5,7-dihydroxy-8-methoxyflavone) on cancer immunogenicity has not been studied. Here we demonstrated for the first time that wogonin elicits a potent antitumor immunity effect by inducing the translocation of calreticulin (CRT) and Annexin A1 to cell plasma membrane as well as the release of high-mobility group protein 1 (HMGB1) and ATP. Signal pathways involved in this process were studied. We found that wogonin-induced reactive oxygen species (ROS) production causes an endoplasmic reticulum (ER) stress response, including the phosphorylation of PERK (PKR-like endoplasmic reticulum kinase)/PKR (protein kinase R) and eIF2α (eukaryotic initiation factor 2α), which served as upstream signal for the activation of phosphoinositide 3-kinase (PI3K)/AKT, inducing calreticulin (CRT)/Annexin A1 cell membrane translocation. P22/CHP, a Ca2+-binding protein, was associated with CRT and was required for CRT translocation to cell membrane. The releases of HMGB1 and ATP from wogonin treated MFC cells, alone or together with other possible factors, activated dendritic cells and induced cytokine releases. In vivo study confirmed that immunization with wogonin-pretreated tumor cells vaccination significantly inhibited homoplastic grafted gastric tumor growth in mice and a possible inflammatory response was involved. In conclusion, the activation of PI3K pathway elicited by ER stress induced CRT/Annexin A1 translocation (“eat me” signal) and HMGB1 release, mediating wogonin-induced immunity of tumor cell vaccine. This indicated that wogonin is a novel effective candidate of immunotherapy against gastric tumor.
Raw and processed Radix Polygoni Multiflori have been used in the prevention and treatment of nonalcoholic fatty liver disease (NAFLD), hyperlipidemia, and related diseases in Asian counties for centuries. The lipid regulation ability of raw and processed Poligoni Multiflori Radix were compared in high-fat diet fed rats in this research. Total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C) in blood and liver tissue were all significantly higher in model rats. However, triglyceride (TG) contents increased only in liver tissue, not in the blood samples. The rats fed the high-fat diets were considered the model of type IIa hyperlipidemia and early-stage nonalcoholic fatty liver disease. Both Radix Polygoni Multiflori (RPM) and Radix Polygoni Multiflori Praeparata (RPMP) revealed TC-lowing effects, and middling doses of RPMP displayed the most significant TC-lowing effects, as indicated by blood samples. Neither RPM nor RPMP was found to reduce LDL-C in rats' blood. Nevertheless, RPM showed dose-dependent TC- and TG-lowing effects in the liver tissue samples. In conclusion, RPM showed more pronounced effects on lipid regulation in liver samples in the treatment of early-stage NAFLD. RPMP, however, displayed better effects in regulating lipids in circulating blood for the treatment of hyperlipidemia.
The purpose of this work is to study the antimetastasis activity of gadolinium metallofullerenol nanoparticles (f-NPs) in malignant and invasive human breast cancer models. We demonstrated that f-NPs inhibited the production of matrix metalloproteinase (MMP) enzymes and further interfered with the invasiveness of cancer cells in tissue culture condition. In the tissue invasion animal model, the invasive primary tumor treated with f-NPs showed significantly less metastasis to the ectopic site along with the decreased MMP expression. In the same animal model, we observed the formation of a fibrous cage that may serve as a physical barrier capable of cancer tissue encapsulation that cuts the communication between cancer- and tumor-associated macrophages, which produce MMP enzymes. In another animal model, the blood transfer model, f-NPs potently suppressed the establishment of tumor foci in lung. Based on these data, we conclude that f-NPs have antimetastasis effects and speculate that utilization of f-NPs may provide a new strategy for the treatment of tumor metastasis.
Nanomedicine; Metallofullerenol nanoparticles; Cancer metastasis; Matrix metalloproteinase; Fibrous cage
Ventilator-associated pneumonia (VAP) is a common and sometimes fatal complication in pediatric intensive care units (PICU). The aim of our study was to characterize the distribution and drug susceptibility of the pathogens isolated from the sputum of patients with VAP in the PICU of our hospital and to provide support to the administration of antibiotics early and reasonably in the clinic. Our study was conducted between January 2007 and December 2011 at the PICU of the Children’s Hospital of Zhejiang University School of Medicine. The endotracheal aspirates were collected and transported to a microbiology laboratory within 15 min. The pathogens were routinely analyzed and identified with Vitek 60 and Kirby-Bauer disk diffusion methods. Among the 121 VAP patients, 127 pathogenic strains were isolated from sputum specimens. Gram-negative and gram-positive bacteria and fungi accounted for 64.57% (82/127), 29.92% (38/127) and 5.51% (7/127), respectively. Acinetobacter baumannii (25.61%), Escherichia coli (20.27%), Stenotrophomonas maltophilia (20.27%), Klebsiella pneumoniae (16.22%) and Pseudomonas aeruginosa (9.46%) were frequently identified isolates among gram-negative bacteria. Staphylococci were susceptible to vancomycin and linezolid. All fungi were sensitive to the antimicrobial agents. The gram-negative bacteria were more prevalent than gram-positive bacteria and fungi in VAP and demonstrated a higher drug resistance. It is important to administer antimicrobial agents early and reasonably for children with VAP. Knowledge of antibiotic resistance and the characteristics of drug resistance is important for VAP prophylaxis and treatment.
pediatric intensive care unit; ventilator associated pneumonia; sputum; drug susceptibility
Background. In China, the use of traditional Chinese medicine (TCM) is very popular, but little is known about how it is integrated with conventional cancer care. We conducted parallel surveys of patients and physicians on TCM utilization. Methods. Two hundred forty-five patients and 72 allopathic physicians at the Fudan University Shanghai Cancer Center completed questions on their use of and attitude towards TCM. Results. Patient mean age was 51, with 60% female. Eighty-three percent of patients had used TCM. Use was greatest for Chinese herbal medicine (CHM; 55.8%). Only 1.3% of patients used acupuncture and 6.8% Qi Gong or Tai Qi. Sixty-three percent of patients notified their oncologist about TCM use. The most common reason for use was to improve immune function. CHM was often used with a goal of treating cancer (66.4%), a use that 57% of physicians agreed with. Physicians were most concerned with interference with treatment, lack of evidence, and safety. Ninety percent of physicians have prescribed herbs and 87.5% have used TCM themselves. Conclusion. The use of TCM by Chinese cancer patients is exceptionally high, and physicians are generally well informed and supportive of patients' use. Botanical agents are much more commonly used than acupuncture or movement-based therapies.
Thermotoga maritima (T. maritima) is a typical thermophile, and its proteome response to environmental temperature changes has yet to be explored. This study aims to uncover the temperature-dependent proteins of T. maritima using comparative proteomic approach. T. maritima was cultured under four temperatures, 60°C, 70°C, 80°C and 90°C, and the bacterial proteins were extracted and electrophoresed in two-dimensional mode. After analysis of gel images, a total of 224 spots, either cytoplasm or membrane, were defined as temperature-dependent. Of these spots, 75 unique bacterial proteins were identified using MALDI TOF/TOF MS. As is well known, the chaperone proteins such as heat shock protein 60 and elongation factor Tu, were up-regulated in abundance due to increased temperature. However, several temperature-dependent proteins of T. maritima responded very differently when compared to responses of the thermophile T. tengcongensis. Intriguingly, a number of proteins involved in central carbohydrate metabolism were significantly up-regulated at higher temperature. Their corresponding mRNA levels were elevated accordingly. The increase in abundance of several key enzymes indicates that a number of central carbohydrate metabolism pathways of T. maritima are activated at higher temperatures.
Outcome-dependent sampling (ODS) study designs are commonly implemented with rare diseases or when prospective studies are infeasible. In longitudinal data settings, when a repeatedly measured binary response is rare, an ODS design can be highly efficient for maximizing statistical information subject to resource limitations that prohibit covariate ascertainment of all observations. This manuscript details an ODS design where individual observations are sampled with probabilities determined by an inexpensive, time-varying auxiliary variable that is related but is not equal to the response. With the goal of validly estimating marginal model parameters based on the resulting biased sample, we propose a semi-parametric, sequential offsetted logistic regressions (SOLR) approach. The SOLR strategy first estimates the relationship between the auxiliary variable and the response and covariate data by using an offsetted logistic regression analysis where the offset is used to adjust for the biased design. Results from the auxiliary variable model are then combined with the known or estimated sampling probabilities to formulate a second offset that is used to correct for the biased design in the ultimate target model relating the longitudinal binary response to covariates. Because the target model offset is estimated with SOLR, we detail asymptotic standard error estimates that account for uncertainty associated with the auxiliary variable model. Motivated by an analysis of the BioCycle Study (Gaskins et al., Effect of daily fiber intake on reproductive function: the BioCycle Study. American Journal of Clinical Nutrition 2009; 90(4): 1061–1069) that aims to describe the relationship between reproductive health (determined by luteinizing hormone levels) and fiber consumption, we examine properties of SOLR estimators and compare them with other common approaches.
outcome-dependent sampling; bias sampling; study design; generalized estimating equations; longitudinal data analysis; binary data
In capillary electrophoresis, sample ions migrate along a micro-capillary filled with a background electrolyte under the influence of an applied electric field. If the sample concentration is sufficiently high, the electrical conductivity in the sample zone could differ significantly from the background. Under such conditions, the local migration velocity of sample ions becomes concentration dependent resulting in a nonlinear wave that exhibits shock like features. If the nonlinearity is weak, the sample concentration profile, under certain simplifying assumptions, can be shown to obey Burgers’ equation (S. Ghosal and Z. Chen Bull. Math. Biol. 2010 72(8), pg. 2047) which has an exact analytical solution for arbitrary initial condition. In this paper, we use a numerical method to study the problem in the more general case where the sample concentration is not small in comparison to the concentration of background ions. In the case of low concentrations, the numerical results agree with the weakly nonlinear theory presented earlier, but at high concentrations, the wave evolves in a way that is qualitatively different.
This study compared birth parameters and the longitudinal course in physical and neurologic development between children with 2 and 3 vessel umbilical cords.
Our study of the Collaborative Perinatal Project included singletons of at least 24 weeks’ gestation with single umbilical artery at birth and no identifiable congenital anomalies. Demographics that were collected included maternal age, race, smoking status, and socioeconomic index. Delivery data included gestational age, birth-weight, Apgar scores, placental weight, and umbilical cord insertion and length. Growth and neurodevelopmental parameters were collected at various intervals from birth to 7 years.
There were 263 infants with isolated single umbilical artery and 41,415 infants with 3 vessel cords. A random effect model that controlled for potential confounders did not show clinically significant differences in the physical and neurodevelopment measures between these groups.
Our study shows no evidence of differential longitudinal physical growth or neurologic outcomes between infants with 2 or 3 vessel cords.
growth; longitudinal; neurodevelopment; single umbilical artery
To estimate the incidence of endometriosis in an operative cohort of women seeking clinical care and in a matched population cohort to delineate more fully the scope and magnitude of endometriosis in the context of and beyond clinical care.
Matched exposure cohort design.
Surgical centers in the Salt Lake City, Utah and San Francisco, California areas.
The operative cohort comprised 495 women undergoing laparoscopy/laparotomy between 2007–2009, while the population cohort comprised 131 women from the surgical centers’ catchment areas.
Main Outcome Measure(s)
Incidence of endometriosis by diagnostic method in the operative cohort and by pelvic magnetic resonance imaged (MRI) disease in the population cohort.
Endometriosis incidence in the operative cohort ranged by two orders of magnitude by diagnostic method: 0.7% for only histology, 7% for only MRI and 41% for visualized disease. Endometriosis staging was skewed toward minimal (58%) and mild disease (15%). The incidence of MRI-diagnosed endometriosis was 11% in the population cohort.
Endometriosis incidence is dependent upon the diagnostic method and choice of sampling framework. Conservatively, 11% of women have undiagnosed endometriosis at the population level with implications for the design and interpretation of etiologic research.
Endometriosis; epidemiology; histology; incidence; laparoscopy; magnetic resonance imaging
In many biomedical and epidemiological studies, data are often clustered due to longitudinal follow up or repeated sampling. While in some clustered data the cluster size is pre-determined, in others it may be correlated to the outcome of subunits, resulting in informative cluster size. When the cluster size is informative, standard statistical procedures that ignore cluster size may produce biased estimates. One attractive framework for modeling data with informative cluster size is the joint modeling approach in which a common set of random effects are shared by both the outcome and cluster size models. In addition to making distributional assumptions on the shared random effects, the joint modeling approach needs to specify the cluster size model. Questions arise as to whether the joint modeling approach is robust to misspecification of the cluster size model. In this paper, we studied both asymptotic and finite-sample characteristics of the maximum likelihood estimators in joint models when the cluster size model is misspecified. We found that using an incorrect distribution for the cluster size may induce small to moderate biases, while using a misspecified functional form for the shared random parameter in the cluster size model results in nearly unbiased estimation of outcome model parameters. We also found that there is little efficiency loss under this model misspecification. A developmental toxicity study was used to motivate the research and to demonstrate the findings.
Shared parameter models; Non-ignorable dropout; Developmental toxicity; Random cluster size; informative number of observations
In traditional Chinese medicine (TCM) clinical practice, ZHENG (also known as syndrome) helps to guide design of individualized treatment strategies. In this study, we investigated the clinical use of ZHENG in TCM-treated cancer patients by systematically analyzing data from all relevant reports in the Chinese-language scientific literature. We aimed to determine the clinical ZHENG distributions in six common cancers (lung, liver, gastric, breast, colorectal, and pancreatic) with the expectation of uncovering a theoretical basis for TCM ZHENG as a clinical cancer treatment. In addition, we also reviewed the molecular basis underlying Xue-Yu (blood stasis), Shi-Re (dampness-heat), Yin-Xu (Yin deficiency), and Pi-Xu (spleen deficiency) ZHENG that are commonly found in cancer patients. The results from our summary study provide insights into the potential utility of TCM ZHENG and may contribute to a better understanding of the molecular basis of TCM ZHENG in cancer.
AIM: To evaluate the safety, efficacy and management of double balloon enteroscopy (DBE) carried out in those aged individuals with suspicious small intestine diseases.
METHODS: DBE is a wonderful invention of the past decade and is widely used as an examination tool for the gastrointestinal tract. From January 2003 to July 2011, data from patients who were ≥ 65 years old and underwent DBE examination in the Nanfang Hospital were included in a retrospective analysis.
RESULTS: Fifty-nine individuals were found and subsequently analyzed. The mean age was 69.63 ± 3.89 years (range 65-84), 34 were males. Indications for DBE were melena/hematochezia (36 cases), abdominal pain (15 cases), diarrhea (3 cases), stool change (1 case), weight loss (1 case), vomiting (2 cases), and debilitation (1 case). The average duration of symptoms was 33.34 ± 64.24 mo. Twenty-seven patients suffered from age-related diseases. Severe complications were not found during and after DBE. Comparison between systolic and diastolic blood pressure before and after DBE was statistically significant (mean ± SD, P < 0.01, P < 0.05, respectively). Small bowel pathologies were found by DBE in 35 patients, definite diagnoses were made in 31 cases, and detection rate and diagnostic yield for DBE were 68.6% and 60.8%, respectively.
CONCLUSION: DBE is a safe and effective method for gastrointestinal examination in the aged population. Aging alone is not a risk factor for elderly patients with suspicious gastrointestinal diseases and thorough preparation prior to the DBE procedure should be made for individuals with multiple diseases especially cardiopulmonary disorders.
Double balloon enteroscopy; Capsule endoscopy; Small bowel diseases; Multiple systematic diseases
Sumoylation is one of the most essential mechanisms of reversible protein post-translational modifications and is a crucial biochemical process in the regulation of a variety of important biological functions. Sumoylation is also closely involved in various human diseases. The accurate computational identification of sumoylation sites in protein sequences aids in experimental design and mechanistic research in cellular biology. In this study, we introduced amino acid hydrophobicity as a parameter into a traditional binary encoding scheme and developed a novel sumoylation site prediction tool termed SUMOhydro. With the assistance of a support vector machine, the proposed method was trained and tested using a stringent non-redundant sumoylation dataset. In a leave-one-out cross-validation, the proposed method yielded an excellent performance with a correlation coefficient, specificity, sensitivity and accuracy equal to 0.690, 98.6%, 71.1% and 97.5%, respectively. In addition, SUMOhydro has been benchmarked against previously described predictors based on an independent dataset, thereby suggesting that the introduction of hydrophobicity as an additional parameter could assist in the prediction of sumoylation sites. Currently, SUMOhydro is freely accessible at http://protein.cau.edu.cn/others/SUMOhydro/.
We consider the problem of electromigration of a sample ion (analyte) within a uniform background electrolyte when the confining channel undergoes a sudden contraction. One example of such a situation arises in microfluidics in the electrokinetic injection of the analyte into a micro-capillary from a reservoir of much larger size. Here, the sample concentration propagates as a wave driven by the electric field. The dynamics is governed by the Nerst–Planck–Poisson system of equations for ionic transport. A reduced one-dimensional nonlinear equation, describing the evolution of the sample concentration, is derived. We integrate this equation numerically to obtain the evolution of the wave shape and determine how the injected mass depends on the sample concentration in the reservoir. It is shown that due to the nonlinear coupling of the ionic concentrations and the electric field, the concentration of the injected sample could be substantially less than the concentration of the sample in the reservoir.
electromigration dispersion; electrokinetic injection; nonlinear waves
Delayed neutrophil apoptosis may be an important factor in the persistent inflammation associated with chronic obstructive pulmonary disease (COPD). Bcl-2 family proteins are important regulators of neutrophil apoptosis. We determined the mRNA levels of pro-apoptotic Bak and anti-aptototic Bcl-xl and Mcl-1 members of the Bcl-2 family in unstimulated peripheral blood neutrophils from patients with mild to moderate COPD and compared these to neutrophils from healthy controls.
Neutrophils were isolated from peripheral blood samples of 47 COPD patients (smokers: N = 24) and 47 healthy controls (smokers: N = 24). Percentages of apoptotic cells were determined at 4, 24, and 36 h for unstimulated neutrophils cultured in vitro. Neutrophil mRNA expression of Bak, Bcl-xl, and Mcl-1 was determined by real-time polymerase chain reaction (PCR). FEV1 (% predicted) and FVC were determined by spirometry and correlations between mRNA levels and lung function parameters were determined.
The percentages of apoptotic cells among unstimulated neutrophils from COPD patients were significantly lower compared to cells from controls after 4, 24, and 36 h in culture; smoking history had only a minimal effect on these differences. Unstimulated neutrophils from COPD patients had significantly lower Bak mRNA expression and higher expressions of Bcl-xl and Mcl-1 mRNA than cells from healthy controls. Again, smoking history had only a minimal effect on these trends. Bak mRNA expression was significantly positively correlated with both % predicted FEV1 and the FEV1/FVC ratio, while Bcl-xl and Mcl-1 mRNA expressions were significantly negatively correlated with %predicted FEV1 and the FEV1/FVC ratio.
The genes for pro-apoptotic Bak, and anti-apoptotic Bcl-xl and Mcl-1 may be important in regulating the delayed neutrophil apoptosis observed in COPD, which may contribute to COPD pathogenesis.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1605269445677066
Apoptosis; Bcl-2; Chronic obstructive pulmonary disease; Lung function; Neutrophils
To assess salivary stress biomarkers (cortisol and alpha-amylase) and female fecundity.
Prospective cohort design.
274 women aged 18–40 years attempting pregnancy were followed until pregnant or for six menstrual cycles. Women collected basal saliva samples on day 6 of each cycle, and used fertility monitors to identify ovulation and pregnancy test kits for pregnancy detection.
Main Outcome Measures
Exposures included salivary cortisol (μg/dL) and alpha-amylase (U/mL) concentrations. Fecundity was measured by time-to-pregnancy and the probability of pregnancy during the fertile window as estimated from discrete-time survival and Bayesian modeling techniques, respectively.
Alpha-amylase but not cortisol concentrations were negatively associated with fecundity in the first cycle (fecundity odds ratio = 0.85; 95% confidence interval 0.67, 1.09) after adjusting for couples’ ages, intercourse frequency, and alcohol consumption. Significant reductions in the probability of conception across the fertile window during the first cycle attempting pregnancy were observed for women whose salivary concentrations of alpha-amylase were in the upper quartiles in comparison to women in the lower quartiles (HPD −0.284; 95% interval −0.540, −0.029).
Stress significantly reduced the probability of conception each day during the fertile window, possibly exerting its effect through the sympathetic medullar pathway.
alpha amylase; conception; cortisol; fecundity; fertile window; stress
Background: An equivocal literature exists regarding the relation between persistent organochlorine pollutants (POPs) and endometriosis in women, with differences attributed to methodologies.
Objectives: We assessed the association between POPs and the odds of an endometriosis diagnosis and the consistency of findings by biological medium and study cohort.
Methods: Using a matched cohort design, we assembled an operative cohort of women 18–44 years of age undergoing laparoscopy or laparotomy at 14 participating clinical centers from 2007 to 2009 and a population-based cohort matched on age and residence within a 50-mile catchment area of the clinical centers. Endometriosis was defined as visualized disease in the operative cohort and as diagnosed by magnetic resonance imaging in the population cohort. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for each POP in relation to an endometriosis diagnosis, with separate models run for each medium (omental fat in the operative cohort, serum in both cohorts) and cohort. Adjusted models included age, body mass index, breast-feeding conditional on parity, cotinine, and lipids.
Results: Concentrations were higher in omental fat than in serum for all POPs. In the operative cohort, γ-hexachlorocyclohexane (γ-HCH) was the only POP with a significant positive association with endometriosis [per 1-SD increase in log-transformed γ-HCH: adjusted OR (AOR) = 1.27; 95% CI: 1.01, 1.59]; β-HCH was the only significant predictor in the population cohort (per 1-SD increase in log-transformed β-HCH: AOR = 1.72; 95% CI: 1.09, 2.72).
Conclusions: Using a matched cohort design, we found that cohort-specific and biological-medium–specific POPs were associated with endometriosis, underscoring the importance of methodological considerations when interpreting findings.
endocrine-disrupting chemicals; organochlorine pesticides; persistent organochlorine pollutants; polybrominated diphenyl ethers; polychlorinated biphenyls
In traditional Chinese medicine (TCM), diagnosis of pathology and choice of treatment prescriptions are based on a method of differentiation of signs and symptoms known as syndrome differentiation or ZHENG. The cornerstone of TCM, ZHENG, relies on the gathering of clinical information through inspection, auscultation and olfaction, inquiry, and palpation. However, the biomolecular basis of the ZHENG remains unclear. In this study, we established mouse xenograft pancreatic cancer models with Shi-Re (Dampness-Heat), Pi-Xu (Spleen-Deficiency), or Xue-Yu (Blood-Stasis) ZHENG, which are regarded as the three major ZHENGs in pancreatic cancer. We found that tumors of the different ZHENG models exhibited significantly altered cancer-associated fibroblast (CAF) proliferative activity and tumor-associated macrophage (TAM) infiltration, which led to altered levels of CAF- and TAM-derived secreted cytokines such as SDF-1 and CCL5. The ZHENG model type also significantly influenced tumor growth, and administration of herbal medicine to the ZHENG model modified the tumor microenvironment. Therefore, this study partially unveiled the molecular basis of TCM ZHENG in pancreatic cancer.
In the structure of the title compound, C7H10OS4Si, the carbonyl O atom lies in the plane of the five-membered dithiole ring with a deviation of only 0.022 (2) Å. The seven-membered ring adopts a chair conformation. The crystal packing is stabilized by S⋯O [3.096 (4) Å] and S⋯S [3.620 (4) Å] contacts, together with C—H⋯S interactions.
In a previous paper (S. Ghosal and Z. Chen Bull. Math. Biol. 2010 72, pg. 2047) it was shown that the evolution of the solute concentration in capillary electrophoresis is described by a nonlinear wave equation that reduced to Burger’s equation if the nonlinearity was weak. It was assumed that only strong electrolytes (fully dissociated) were present. In the present paper it is shown that the same governing equation also describes the situation where the electrolytic buffer consists of a single weak acid (or base). A simple approximate formula is derived for the dimensionless peak variance which is shown to agree well with published experimental data.
capillary electrophoresis; electromigration dispersion