We aimed to evaluate the performance of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine–cystatin C equation in a cohort of elderly Chinese participants.
Materials and methods
Glomerular filtration rate (GFR) was measured in 431 elderly Chinese participants by the technetium-99m diethylene-triamine-penta-acetic acid (99mTc-DTPA) renal dynamic imaging method, and was calibrated equally to the dual plasma sample 99mTc-DTPA-GFR. Performance of the CKD-EPI creatinine–cystatin C equation was compared with the Cockcroft–Gault equation, the re-expressed 4-variable Modification of Diet in Renal Disease (MDRD) equation, and the CKD-EPI creatinine equation.
Although the bias of the CKD-EPI creatinine–cystatin C equation was greater than with the other equations (median difference, 5.7 mL/minute/1.73 m2 versus a range from 0.4–2.5 mL/minute/1.73 m2; P<0.001 for all), the precision was improved with the CKD-EPI creatinine–cystatin C equation (interquartile range for the difference, 19.5 mL/minute/1.73 m2 versus a range from 23.0–23.6 mL/minute/1.73 m2; P<0.001 for all comparisons), leading to slight improvement in accuracy (median absolute difference, 10.5 mL/minute/1.73 m2 versus 12.2 and 11.4 mL/minute/1.73 m2 for the Cockcroft–Gault equation and the re-expressed 4-variable MDRD equation, P=0.04 for both; 11.6 mL/minute/1.73 m2 for the CKD-EPI creatinine equation, P=0.11), as the optimal scores of performance (6.0 versus a range from 1.0–2.0 for the other equations). Higher GFR category and diabetes were independent factors that negatively correlated with the accuracy of the CKD-EPI creatinine–cystatin C equation (β=−0.184 and −0.113, P<0.001 and P=0.02, respectively).
Compared with the creatinine-based equations, the CKD-EPI creatinine–cystatin C equation is more suitable for the elderly Chinese population. However, the cost-effectiveness of the CKD-EPI creatinine–cystatin C equation for clinical use should be considered.
elderly; equation; glomerular filtration rate; serum creatinine; cystatin C
Pruning that selectively eliminates unnecessary axons/dendrites is crucial for sculpting the nervous system during development. During Drosophila metamorphosis, dendrite arborization neurons, ddaCs, selectively prune their larval dendrites in response to the steroid hormone ecdysone, whereas mushroom body γ neurons specifically eliminate their axon branches within dorsal and medial lobes. However, it is unknown which E3 ligase directs these two modes of pruning. Here, we identified a conserved SCF E3 ubiquitin ligase that plays a critical role in pruning of both ddaC dendrites and mushroom body γ axons. The SCF E3 ligase consists of four core components Cullin1/Roc1a/SkpA/Slimb and promotes ddaC dendrite pruning downstream of EcR-B1 and Sox14, but independently of Mical. Moreover, we demonstrate that the Cullin1-based E3 ligase facilitates ddaC dendrite pruning primarily through inactivation of the InR/PI3K/TOR pathway. We show that the F-box protein Slimb forms a complex with Akt, an activator of the InR/PI3K/TOR pathway, and promotes Akt ubiquitination. Activation of the InR/PI3K/TOR pathway is sufficient to inhibit ddaC dendrite pruning. Thus, our findings provide a novel link between the E3 ligase and the InR/PI3K/TOR pathway during dendrite pruning.
Neurons have the ability to engage in selective pruning that eliminates unnecessary axons/dendrites. This process is crucial for sculpting the nervous system during development. During Drosophila development, dendrite arborization sensory neurons (ddaCs) selectively prune their larval dendrites in response to the molting steroid hormone ecdysone, whereas mushroom body γ neurons eliminate their axon branches. However, the underlying molecular mechanisms for both of these modes of pruning were not well understood. Here, we conduct a genome-wide screen and identify a conserved E3 ubiquitin ligase that is critical for pruning both ddaC dendrites and mushroom body γ axons. This ligase complex has four core components—Cullin1, Roc1a, SkpA, and Slimb—that promote ddaC dendrite pruning in response to ecdysone. We show that this ligase facilitates ddaC dendrite pruning through regulation of the InR/PI3K/TOR pathway. The substrate-recognition protein Slimb promotes ubiquitination of Akt, an activator of the InR/PI3K/TOR pathway. Akt ubiquitination leads to its degradation and inactivation of the InR/PI3K/TOR pathway, which is required for dendritic pruning. Consistent with this, ddaC dendrite pruning is inhibited when the InR/PI3K/TOR pathway is activated. Thus, we identify a link between the Cullin1-based E3 ligase and the InR/PI3K/TOR pathway in regulating dendrite pruning. This work represents the first link between neuronal pruning and the insulin signaling pathway, raising interesting questions about how metabolic states may influence the control of such developmental processes.
Lung cancer is one of the leading causes of cancer-related mortality worldwide. Gastrointestinal metastasis from primary lung cancer is rare. Only a few reports have been published and the majority of described metastatic sites involved the small intestine. In the present study, we report the first case of primary lung adenocarcinoma with both gastric and colonic metastases. We also review the published literature of primary lung cancer with gastrointestinal metastasis.
lung cancer; gastrointestinal metastasis
Herpes simplex virus 2 (HSV-2) infection is still one of the common causes of sexually transmitted diseases worldwide. The prevalence of HSV strains resistant to traditional nucleoside antiviral agents has led to the development of novel antiviral drugs. Human alpha-defensin 5 (HD5), a kind of endogenous antimicrobial peptide expressed in the epithelia of the small intestine and urogenital tract, displays natural antiviral activity. Based on arginine-rich features and adaptive evolution characteristics of vertebrate defensins, we conducted a screen for HD5 derivatives with enhanced anti-HSV-2 activity by a single arginine substitution at the adaptive evolution sites. Cell protection assay and temporal antiviral studies showed that HD5 and its mutants displayed affirmatory but differential anti-HSV-2 effects in vitro by inhibiting viral adhesion and entry. Inspiringly, the E21R-HD5 mutant had significantly higher antiviral activity than natural HD5, which is possibly attributed to the stronger binding affinity of the E21R-HD5 mutant with HSV-2 capsid protein gD, indicating that E21R mutation can increase the anti-HSV-2 potency of HD5. In a mouse model of lethal HSV-2 infection, prophylactic and/or therapeutic treatment with E21R-HD5 via intravaginal instillation remarkably alleviated the symptoms and delayed disease progress and resulted in about a 1.5-fold-higher survival rate than in the HD5 group. Furthermore, the E21R variant exhibited a 2-fold-higher antiviral potency against HIV-1 over parental HD5 in vitro. This study demonstrates that arginine mutagenesis at appropriate evolution sites may significantly enhance the antiviral activity of HD5, which also paves a facile way to search for potent antiviral drugs based on natural antimicrobial peptides.
To determine the prevalence and correlates of syphilis among pregnant women in rural areas of South China.
Point-of-care syphilis testing was provided at 71 health facilities in less developed, rural areas of Guangdong Province. Positive samples were confirmed at a local referral center by toluidine red unheated serum tests (TRUST) and Treponema pallidum particle agglutination (TPPA) tests.
Altogether 27,150 pregnant women in rural Guangdong were screened for syphilis. 106 (0.39%) syphilis cases were diagnosed, of which 78 (73.6%) received treatment for syphilis. Multivariate analysis revealed that older pregnant women (31–35 years old, aOR 2.7, 95% CI 0.99–7.32; older than 35 years old, aOR 5.9, 95% CI 2.13–16.34) and those with a history of adverse pregnant outcomes (aOR 3.64, 95% CI 2.30–5.76) were more likely to be infected with syphilis.
A high prevalence of syphilis exists among pregnant women living in rural areas of South China. Enhanced integration of syphilis screening with other routine women's health services (OB GYN, family planning) may be useful for controlling China's syphilis epidemic.
Accurate and precise estimates of glomerular filtration rate (GFR) are essential for clinical assessments, and many methods of estimation are available. We developed a radial basis function (RBF) network and assessed the performance of this method in the estimation of the GFRs of 207 patients with type-2 diabetes and CKD.
Standard GFR (sGFR) was determined by 99mTc-DTPA renal dynamic imaging and GFR was also estimated by the 6-variable MDRD equation and the 4-variable MDRD equation.
Bland-Altman analysis indicated that estimates from the RBF network were more precise than those from the other two methods for some groups of patients. However, the median difference of RBF network estimates from sGFR was greater than those from the other two estimates, indicating greater bias. For patients with stage I/II CKD, the median absolute difference of the RBF network estimate from sGFR was significantly lower, and the P50 of the RBF network estimate (n = 56, 87.5%) was significantly higher than that of the MDRD-4 estimate (n = 49, 76.6%) (p < 0.0167), indicating that the RBF network estimate provided greater accuracy for these patients.
In patients with type-2 diabetes mellitus, estimation of GFR by our RBF network provided better precision and accuracy for some groups of patients than the estimation by the traditional MDRD equations. However, the RBF network estimates of GFR tended to have greater bias and higher than those indicated by sGFR determined by 99mTc-DTPA renal dynamic imaging.
Type 2 diabetes; Chronic kidney disease; Glomerular filtration rate; Artificial neural network
Three new bicyclic depsipeptides, which are related to the previously reported thailandepsins A (1), B (2) and C (3), were discovered from the culture broth of Burkholderia thailandensis E264 when supplemented with amino acid precursors, and were subsequently named as thailandepsins D (4), E (5) and F (6), respectively. Enzyme assays showed that 1–6 are potent histone deacetylase (HDAC) inhibitors, particularly toward HDAC1 which represents class I human HDACs.
Cellular reprogramming of somatic cells to patient-specific induced pluripotent stem cells (iPSCs) enables in-vitro modelling of human genetic disorders for pathogenic investigations and therapeutic screens1–7. However, using iPSC-derived cardiomyocytes (iPSC-CMs) to model an adult-onset heart disease remains challenging due to the uncertainty regarding the ability of relatively immature iPSC-CMs to fully recapitulate adult disease phenotypes. Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited heart disease characterized by pathological fatty infiltration and cardiomyocyte loss predominantly in the right ventricle (RV)8, which is associated with life-threatening ventricular arrhythmias. Over 50% of affected individuals have desmosome gene mutations, most commonly in PKP2 encoding plakophilin-29. The median age at presentation of ARVD/C is 26 years8. We used Yamanaka’s methods1,10 to generate iPSC lines from fibroblasts of two patients with ARVD/C and PKP2 mutations11,12. Mutant PKP2 iPSC-CMs demonstrate abnormal plakoglobin nuclear translocation and decreased β-catenin activity13 in cardiogenic conditions; yet these abnormal features are insufficient to reproduce the pathological phenotypes of ARVD/C in standard cardiogenic conditions. Here we show that induction of adult-like metabolic energetics from an embryonic/glycolytic state and abnormal peroxisome proliferator-activated receptor-gamma (PPARγ) activation underlie the pathogenesis of ARVD/C. By coactivating normal PPAR-alpha (PPARα)-dependent metabolism and abnormal PPARγ pathway in beating embryoid bodies (EBs) with defined media, we established an efficient ARVD/C in-vitro model within two months. This model manifests exaggerated lipogenesis and apoptosis in mutant PKP2 iPSC-CMs. iPSC-CMs with a homozygous PKP2 mutation also displayed calcium-handling deficits. Our study is the first to demonstrate that induction of adult-like metabolism plays a critical role in establishing an adult-onset disease model using patient-specific iPSCs. Using this model, we revealed crucial pathogenic insights that metabolic derangement in adult-like metabolic milieu underlies ARVD/C pathologies, enabling us to propose novel disease-modifying therapeutic strategies.
The purpose of our study is to investigate whether diffusion-weighted imaging (DWI) is useful for monitoring the therapeutic response after neoadjuvant chemotherapy in osteosarcoma of long bones.
Materials and methods
Conventional magnetic resonance imaging (MRI) and DWI were obtained from 35 patients with histologically proven osteosarcomas. MR examinations were performed in all patients before and after 4 courses of preoperative neoadjuvant chemotherapy. Apparent diffusion coefficients (ADC) were measured. The degree of tumor necrosis was assessed macroscopically and histologically by two experienced pathologists after operation. Student’s t test was performed for testing changes in ADC value. Pearson’s correlation coefficient was used to estimate the correlation between necrosis rate and post- neoadjuvant chemotherapy ADC values. P<0.05 was considered to denote a significant difference.
The difference of the whole osteosarcoma between pre- neoadjuvant chemotherapy ADC value (1.24±0.17×10−3 mm2/s) and post- (1.93±0.39×10−3 mm2/s) was significant difference (P<0.01). Regarding in patients with good response, the post- neoadjuvant chemotherapy values were significantly higher than the pre- neoadjuvant chemotherapy values (P<0.01). The post- neoadjuvant chemotherapy ADC value in patients with good response was higher than that of poor response (t = 8.995, P<0.01). The differences in post- neoadjuvant chemotherapy ADC between viable (1.03±0.17×10−3 mm2/s) and necrotic (2.38±0.25×10−3 mm2/s) tumor was highly significant (t = 23.905, P<0.01). A positive correlation between necrosis rates and the whole tumor ADC values (r = 0.769, P<0.01) was noted, but necrosis rates were not correlated with the ADC values of necrotic (r = −0.191, P = 0.272) and viable tumor areas (r = 0.292, P = 0.089).
DWI can identify residual viable tumor tissues and tumor necrosis induced by neoadjuvant chemotherapy in osteosarcoma. The ADC value can directly reflect the degree of tumor necrosis, and it is useful to evaluate the preoperative neoadjuvant chemotherapy response in patients with osteosarcoma.
Background. The prognostic significance of ERG expression in prostate cancer (PCA) has generated mixed results. We sought to investigate the prognostic significance of ERG expression in a localized cohort of men with PCA. Material and Methods. We investigated ERG protein expression in a cohort of 198 men with localized PCA. ERG expression was correlated with patients' clinical outcome and several pathological parameters, including Gleason score (GS), pathological stage, surgical margin, and extra-capsular extension. Results. ERG expression was detected in 86/198 (43.4%) patients exclusively in neoplastic epithelium. Overall, ERG mean expression intensity was 1.01 ± 1.27 versus 0.37 ± 0.83 in acinar PCA compared to foamy type PCA (P < 0.001). In HGPIN, ERG intensity levels were comparable to those in foamy type PCA (0.13 ± 0.56) but significantly lower than those in acinar PCA (P < 0.001). ERG expression was significantly associated with extra-prostatic extension and higher pathological stage and showed a trend toward seminal vesicle invasion. Herein, ERG expression was documented in 50/131 (38.1%) patients with pT2 versus 30/55 (54.5%) patients with pT3 (P = 0.04). ERG association with higher pathological stage was more pronounced in patients with GS > 7. Grouping patients into those with GS ≤ 7 versus >7, there was no significant association between ERG expression and GS. Similarly, no association was present in relation to either surgical margins or postsurgical serum PSA levels. Conclusion. We report significant association between ERG protein levels and extra-prostatic extension and higher pathological stage. ERG expression is not associated with adverse clinical outcome and is of limited prognostic value in localized PCA.
Female sex workers have been the target of numerous sexually transmitted infection (STI) prevention strategies in China, but their male clients have attracted considerably less public health attention and resources. We sought to systematically assess the prevalence of HIV, syphilis, gonorrhea, and chlamydia among heterosexual male clients of female sex workers in China.
Original research manuscripts were identified by searching Chinese and English language databases, and 37 studies analyzing 26,552 male clients were included in the review. Client STI prevalence across studies was heterogeneous. Pooled prevalence estimates and 95% confidence intervals were 0.68% (0.36–1.28%) for HIV, 2.91% (2.17–3.89%) for syphilis, 2.16% (1.46–3.17%) for gonorrhea, and 8.01% (4.94–12.72%) for chlamydia.
The pooled prevalence estimates of HIV, syphilis, gonorrhea, and chlamydia among clients in this review exceed the prevalences previously reported among population-representative samples and low-risk groups in China. However, heterogeneity across studies and sampling limitations prevent definitive conclusions about how the prevalence of STIs in this population compares to the general population. These findings suggest a need for greater attention to clients’ sexual risk and disease prevalence in China’s STI research agenda in order to inform effective prevention policies.
Baylisascaris schroederi is one of the most common nematodes of the giant panda, and can cause severe baylisascarosis in both wild and captive giant pandas. Previous studies of the giant pandas indicated that this population is genetically distinct, implying the presence of a new subspecies. Based on the co-evolution between the parasite and the host, the aim of this study was to investigate the genetic differentiation in the B. schroederi population collected from giant pandas inhabiting different mountain ranges, and further to identify whether the evolution of this parasite correlates with the evolution of giant pandas.
In this study, 48 B. schroederi were collected from 28 wild giant pandas inhabiting the Qinling, Minshan and Qionglai mountain ranges in China. The complete sequence of the mitochondrial cytochrome b (mtCytb) gene was amplified by PCR, and the corresponding population genetic diversity of the three mountain populations was determined. In addition, we discussed the evolutionary relationship between B. schroederi and its host giant panda.
For the DNA dataset, insignificant Fst values and a significant, high level of gene flow were detected among the three mountain populations of B. schroederi, and high genetic variation within populations and a low genetic distance were observed. Both phylogenetic analyses and network mapping of the 16 haplotypes revealed a dispersed pattern and an absence of branches strictly corresponding to the three mountain range sampling sites. Neutrality tests and mismatch analysis indicated that B. schroederi experienced a population expansion in the past.
Taken together, the dispersed haplotype map, extremely high gene flow among the three populations of B. schroederi, low genetic structure and rapid evolutionary rate suggest that the B. schroederi populations did not follow a pattern of isolation by distance, indicating the existence of physical connections before these populations became geographically separated.
Giant panda; Baylisascaris schroederi; Mountain ranges; Genetic diversity; Genetic structure; Phylogeography
MicroRNA deregulation is a critical event in head and neck squamous cell carcinoma (HNSCC). Several microRNA profiling studies aimed at deciphering the microRNA signatures of HNSCC have been reported, but there tends to be poor agreement among studies. The objective of this study was to survey the published microRNA profiling studies on HNSCC, and to assess the commonly deregulated microRNAs in an independent sample set.
Materials and Methods
Meta-analysis of 13 published microRNA profiling studies was performed to define microRNA signatures in HNSCC. Selected microRNAs (including members of miR-99 family) were evaluated in an independent set of HNSCC cases. The potential contributions of miR-99 family to the tumorigenesis of HNSCC were assessed by in vitro assays.
We identified 67 commonly deregulated microRNAs. The up-regulation of miR-21, miR-155, miR-130b, miR-223 and miR-31, and the down-regulation of miR-100, miR-99a and miR-375 were further validated in an independent set of HNSCC cases with quantitative RT-PCR. Among these validated microRNAs, miR-100 and miR-99a belong to the miR-99 family. Our in vitro study demonstrated that restoration of miR-100 to the HNSCC cell lines suppressed cell proliferation and migration, and enhanced apoptosis. Furthermore, ectopic transfection of miR-99 family members down-regulated the expression of insulin-like growth factor 1 receptor (IGF1R) and mechanistic target of rapamycin (mTOR) genes.
In summary, we described a panel of frequently deregulated microRNAs in HNSCC, including members of miR-99 family. The deregulation of miR-99 family contributes to the tumorigenesis of HNSCC, in part by targeting IGF1R and mTOR signaling pathways.
meta-analysis; HNSCC; microRNA profiling; miR-99 family; miR-100; IGF1R; mTOR; tumor suppressor
The aim of the present study was to evaluate modified glomerular filtration rate (GFR) prediction formulae in an elderly Chinese population with chronic kidney disease (CKD).
A total of 378 elderly Chinese patients with CKD were enrolled. The GFR was estimated with six modified GFR prediction formulae. The performances of the estimated GFRs were compared with those of the standard GFRs measured by technetium-99m diethyl-enetraminepentaacetic acid.
Biases were similar for Chinese formula 1, the Asian formula, and Chinese formula 2 (median difference, 2.22 mL/min/1.73 m2 and 2.59 mL/min/1.73 m2 for Chinese formula 1 and the Asian formula, respectively, versus (vs) 3.69 mL/min/1.73 m2 for Chinese formula 2 [P = 0.298 and P = 0.913, respectively]). Precision was improved with the Japanese formula (interquartile range of the difference, 3.14 mL/min/1.73 m2 of the Japanese formula versus 15.53–23.06 mL/min/1.73 m2 of the other formulae). The accuracy of Chinese formula 2 was the highest (30% accuracy, 59.3% vs range 37.8–54.0% [P < 0.05 for all comparisons]). However, none of the modified formulae surpassed the acceptable tolerance (>70%), and the GFR category misclassification rates for all the formulae exceeded 50%.
Our findings suggest that all six modified formulae developed in Asian populations may show great bias in elderly Chinese patients with CKD. Also, our study suggests the need for uniform measures for the assessment of CKD in the elderly to guarantee better sensitivity and specificity.
formula; CKD; Asian; GFR
Dioscorea tuber phytoextracts can confer immunomodulatory activities ex vivo and improve regeneration of bone marrow cells in vivo. In present study, we evaluated specific Dioscorea phytoextracts for use ex vivo as a bone-marrow-derived dendritic cell- (DC-) based vaccine adjuvant for cancer immunotherapy. Fractionated Dioscorea extracts (DsII) were assayed for their effect on maturation and functions of DC ex vivo and antimelanoma activity of DC-based vaccine in vivo. The phytoextract from 50–75% ethanol-precipitated fraction of Dioscorea alata var. purpurea Tainung no. 5 tuber, designated as DsII-TN5, showed a strong augmentation of tumor cell lysate- (TCL-) loaded DC-mediated activation of T-cell proliferation. DsII-TN5 stimulated the expression of CD40, CD80, CD86, and IL-1β in TCL-loaded DCs and downregulated the expression of TGF-β1. DC vaccines prepared by a specific schema (TCL (2 h) + LPS (22 h)) showed the strongest antitumor activity. DsII-TN5 as a DC vaccine adjuvant showed strong antimelanoma activity and reduced myeloid-derived suppressor cell (MDSC) population in tested mice. DsII-TN5 can also activate DCs to enhance Th1- and Th17-related cytokine expressions. Biochemical analysis showed that DsII-TN5 consists mainly of polysaccharides containing a high level (53%) of mannose residues. We suggest that DsII-TN5 may have potential for future application as a potent, cost-effective adjuvant for DC-based cancer vaccines.
Aims. To evaluate the efficacy of Chinese herbal medicines (CHMs) plus conventional treatment in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). Methods and Results. Participants (n = 808) with ACS who underwent PCI from thirteen hospitals of mainland China were randomized into two groups: CHMs plus conventional treatment group (treatment group) or conventional treatment alone group (control group). All participants received conventional treatment, and participants in treatment group additionally received CHMs for six months. The primary endpoint was the composite of cardiac death, nonfatal recurrent MI, and ischemia-driven revascularization. Secondary endpoint was the composite of readmission for ACS, stroke, or congestive heart failure. The safety endpoint involved occurrence of major bleeding events. The incidence of primary endpoint was 2.7% in treatment group versus 6.2% in control group (HR, 0.43; 95% CI, 0.21 to 0.87; P = 0.015). The incidence of secondary endpoint was 3.5% in treatment group versus 8.7% in control group (HR, 0.39; 95% CI, 0.21 to 0.72; P = 0.002). No major bleeding events were observed in any participant. Conclusion. Treatment with CHMs plus conventional treatment further reduced the occurrence of cardiovascular events in patients with ACS after PCI without increasing risk of major bleeding.
Diabetic patients, through incompletely understood mechanisms, endure exacerbated ischemic heart injury compared to non-diabetic patients. Intermedin (IMD) is a novel calcitonin gene-related peptide (CGRP) superfamily member with established cardiovascular protective effects. However, whether IMD protects against diabetic myocardial ischemia/reperfusion (MI/R) injury is unknown.
Diabetes was induced by streptozotocin in Sprague–Dawley rats. Animals were subjected to MI via left circumflex artery ligation for 30 minutes followed by 2 hours R. IMD was administered formally 10 minutes before R. Outcome measures included left ventricular function, oxidative stress, cellular death, infarct size, and inflammation.
IMD levels were significantly decreased in diabetic rats compared to control animals. After MI/R, diabetic rats manifested elevated intermedin levels, both in plasma (64.95 ± 4.84 pmol/L, p < 0.05) and myocardial tissue (9.8 ± 0.60 pmol/L, p < 0.01) compared to pre-MI control values (43.62 ± 3.47 pmol/L and 4.4 ± 0.41). IMD administration to diabetic rats subjected to MI/R decreased oxidative stress product generation, apoptosis, infarct size, and inflammatory cytokine release (p < 0.05 or p < 0.01).
By reducing oxidative stress, inflammation, and apoptosis, IMD may represent a promising novel therapeutic target mitigating diabetic ischemic heart injury.
Intermedin; Ischemia-reperfusion; Diabetes; Oxidative stress; Apoptosis; Inflammatory
TP53 is one of the most important prognostic factors in chronic lymphocytic leukemia (CLL). Modulation of microRNAs by TP53 in CLL pathogenesis has been a hotspot. Besides, it has an intimate association with other cytogenetics and plays an important part in drug resistance of CLL. All above indicate an embedded TP53-centered network in CLL pathogenesis and prognosis. In this review, we focus on the TP53-centered network and its roles in the pathogenesis of CLL.
TP53 network; microRNAs; chronic lymphocytic leukemia; pathogenesis
Soybean fermentation broth (SFB) exhibits potent antibacterial activity against different species of bacteria in in vitro assays and animal models. Four isoflavone compounds—daidzin, genistin, genistein, and daidzein—of SFB were analyzed and quantified by high-performance liquid chromatography. In the in vitro test, daidzin and daidzein had more potent antibacterial activity than genistin. The minimum inhibition concentration values for these bacteria of SFB ranged from 1.25% to 5%, and the minimum bactericidal concentration values of strains ranged from 2.5% to 10%, depending on the species or strain. Vancomycin-resistant Entercoccus faecalis (VRE) strains were also tested for susceptibility to SFB in two species of animal model: the Sprague–Dawley rat and the BALB/c mouse. SFB-fed Sprague–Dawley rats showed excellent elimination efficiency against VRE, close to 99% compared with the phosphate-buffered saline–fed control group. In the BALB/c mouse model, SFB antibacterial activity was 65–80% against VRE compared with the control. In conclusion, SFB contains natural antibacterial substances such as daidzin, genistin, and daidzein that inhibit bacterial growth.
animal models; antibacterial activity; isoflavones; soybean fermentation broth; vancomycin-resistant Entercoccus faecalis
The members of the Snail superfamily of zinc-finger transcription factors, including Snai1 and Snai2, are involved in essential biological processes, such as epithelial-mesenchymal transition (EMT). While Snai1 has been investigated in a number of cancers, our knowledge on Snai2 and its role(s) in squamous cell carcinoma of oral tongue (SCCOT) is limited. In this study, we confirmed the previous observation that over-expression of Snai2 is a frequent event in SCCOT. We further demonstrated that Snai2 over-expression is associated with lymph node metastasis in two independent SCCOT patient cohorts (total n = 129). Statistical analysis revealed that Snai2 over-expression was correlated with reduced overall survival. Furthermore, over-expression of Snai2 was correlated with reduced E-cadherin expression and enhanced Vimentin expression, suggesting a functional role of Snai2 in EMT. These observations were confirmed in vitro, in which knockdown of Snai2 induced a switch from a mesenchymal-like morphology to an epithelial-like morphology in SCCOT cell lines, and suppressed the cell invasion and migration. In contrast, ectopic transfection of Snai2 led to enhanced cell invasion and migration. Furthermore, Snai2 knockdown attenuated TGFβ1-induced EMT in SCCOT cell lines. Taken together, these data suggest that Snai2 plays major roles in EMT and the progression of SCCOT, and may serve as a therapeutic target for patients at risk of metastasis.
epithelial menschymal transition; E-cadherin; Snai2; squmous cell carcinoma
Based on Social Penetration theory, this study explores the topics that bloggers disclose on their blogs, and in the real world. A total of 1,027 Taiwanese bloggers participated in this online survey, which revealed that bloggers self-disclosed nine topics (attitude, body, money, work, feelings, personal, interests, experiences, and unclassified). Further, we examined the depth and width of what bloggers self-disclosed to three target audiences (online audience, best friend, and parents), confirming that their disclosure is significantly different for each of these target audiences. Bloggers seemingly express themselves to their best friends the most, followed by parents and online audiences, both in depth and in width. The “wedge model,” proposed by Altman and Taylor (1973), has been extended to online relationships in this study. In comparison to male bloggers, female bloggers seemed to disclose more to their best friends and parents in their daily lives; however, no significant difference was observed in their disclosure to online audiences. Younger bloggers (<20 years old) seemed to disclose a wider range of topics; however, there was no significant difference in the depth of their disclosure on their blogs. Discussions of these results are also presented.
Runs of homozygosity (ROHs) are a class of important but poorly studied genomic variations and may be involved in individual susceptibility to diseases. To better understand ROH and its relationship with lung cancer, we performed a genome-wide ROH analysis of a subset of a previous genome-wide case-control study (1,473 cases and 1,962 controls) in a Han Chinese population. ROHs were classified into two classes, based on lengths, intermediate and long ROHs, to evaluate their association with lung cancer risk using existing genome-wide single nucleotide polymorphism (SNP) data. We found that the overall level of intermediate ROHs was significantly associated with a decreased risk of lung cancer (odds ratio = 0.63; 95% confidence interval: 0.51-0.77; P = 4.78×10−6 ), while the long ROHs seemed to be a risk factor of lung cancer. We also identified one ROH region at 14q23.1 that was consistently associated with lung cancer risk in the study. These results indicated that ROHs may be a new class of variation which may be associated with lung cancer risk, and genetic variants at 14q23.1 may be involved in the development of lung cancer.
lung cancer; runs of homozygosity (ROHs); genome-wide association study
Apoptosis plays a key role in inhibiting tumor growth, progression and resistance to anti-tumor therapy. We hypothesized that genetic variants in apoptotic genes may affect the prognosis of lung cancer. To test this hypothesis, we selected 38 potentially functional single nucleotide polymorphisms (SNPs) from 12 genes (BAX, BCL2, BID, CASP3, CASP6, CASP7, CASP8, CASP9, CASP10, FAS, FASLG and MCL1) involved in apoptosis to assess their prognostic significance in lung cancer in a Chinese case cohort with 568 non-small cell lung cancer (NSCLC) patients. Thirty-five SNPs passing quality control underwent association analyses, 11 of which were shown to be significantly associated with NSCLC survival (P < 0.05). After Cox stepwise regression analyses, 3 SNPs were independently associated with the outcome of NSCLC (BID rs8190315: P = 0.003; CASP9 rs4645981: P = 0.007 and FAS rs1800682: P = 0.016). A favorable survival of NSCLC was significantly associated with the genotypes of BID rs8190315 AG/GG (adjusted HR = 0.65, 95% CI: 0.49-0.88), CASP9 rs4645981 AA (HR = 0.22, 95% CI: 0.07-0.69) and FAS rs1800682 GG (adjusted HR = 0.67, 95% CI: 0.46-0.97). Time-dependent receptor operation curve (ROC) analysis revealed that the area under curve (AUC) at year 5 was significantly increased from 0.762 to 0.819 after adding the risk score of these 3 SNPs to the clinical risk score. The remaining 32 SNPs were not significantly associated with NSCLC prognosis after adjustment for these 3 SNPs. These findings indicate that BID rs8190315, CASP9 rs4645981 and FAS rs1800682 polymorphisms in the apoptotic pathway may be involved in the prognosis of NSCLC in the Chinese population.
apoptosis; polymorphisms; non-small cell lung cancer (NSCLC); prognosis