Summary
Neopterin is primarily synthesized and released by activated macrophages/monocytes upon stimulation with interferon‐γ and is considered as a marker for macrophage activation. This study aimed ...to analyze the serum levels of neopterin in patients with dermatomyositis (DM) in association with clinical manifestations, laboratory data and patient prognosis. One hundred and eighty‐two consecutive DM patients and 30 healthy controls were retrospectively enrolled into the study. Serum levels of neopterin were significantly increased in DM patients compared to healthy controls (P < 0·001). High serum neopterin levels were associated with anti‐melanoma differentiation‐associated gene (MDA5) antibody, rapidly progressive interstitial lung disease (RP‐ILD) and characteristic DM cutaneous involvement. Longitudinal assessment of serum samples revealed that the serum neopterin levels were closely correlated with disease severity (β = 30·24, P < 0·001). In addition, a significant increase in serum neopterin concentration of non‐survivors was observed when compared to that of survivors (P < 0·001). Receiver operator characteristic curves showed that serum neopterin could distinguish non‐survivors and survivors at an optimal cut‐off level of 22·1 nmol/l with a sensitivity and specificity of 0·804 and 0·625, respectively (P < 0·001). Kaplan–Meier survival curves revealed that DM patients with serum neopterin > 22·1 nmol/l had a significantly higher mortality compared to the patient group with serum neopterin < 22·1 nmol/l (log‐rank P < 0·001). Multivariate regression analysis identified high serum neopterin concentration to be an independent risk factor for poor prognosis in DM (adjusted hazard ratio = 4·619, 95% confidence interval = 2·092–10·195, P < 0·001). In conclusion, increased serum levels of neopterin were significantly associated with RP‐ILD and reduced survival in DM patients, suggesting it as a promising biomarker in disease evaluation of DM.
Serum neopterin was significantly increased in DM, especially in patients with anti‐MDA5 and RP‐ILD. Serum neopterin seems to parallel disease severity in DM patients. High baseline level of neopterin was associated with increased mortality and was identified as an independent prognostic factor in DM.
Summary
Our study demonstrated a high incidence of recollapse of the augmented vertebrae after PVP treatment for OVCFs. A risk score based on all significant factors can predict the rate of ...recollapse and gain clinical benefits to prevent recollapse in patients at high risk.
Background
Recollapse of the augmented vertebrae after percutaneous vertebroplasty (PVP) treatment for osteoporotic vertebral compression fractures (OVCFs) has obtained much attention. However, little is known about risk factors and score for recollapse of the augmented vertebrae.
Objective
To determine risk factors and furthermore develop a risk score related to recollapse of the augmented vertebrae after PVP treatment for OVCFs.
Methods
Patients who were treated with PVP for single OVCFs and met this study’s inclusion criteria were retrospectively reviewed. The follow-up period was at least 2 years. Associations of recollapse with co-variates (age, gender, bone mass density BMD with a T-score, fracture level, intravertebral cleft IVC, fracture type, cement volume, cement leakage, leakage into a disc, cement distribution pattern, Non-PMMA-endplate-contact NPEC, preoperative fracture severity, reduction rate RR, reduction angle RA) were analyzed and a risk score for recollapse was further developed to predict recollapse.
Results
A total of 152 patients were included. Recollapse group was found in 42 (27.6%) patients. Preoperative IVC, solid lump cement distribution pattern, more RR (a cutoff value of 7%) and larger RA (a cutoff value of 3°) was significantly associated with increased risk for recollapse of the augmented vertebrae. A risk score was developed based on the number of risk factors present in each patient. Patients with a score of 4 had an approximately ninefold increased risk of developing recollapse over patients with a score of 0. The receiver operating characteristic curve of the risk score generated an area under the curve of 0.899 (95% CI 0.642–0.836,
P
= 0.000).
Conclusion
A risk score based on preoperative IVC, cement distribution pattern, reduction rate, and reduction angle predicts the rate of recollapse. Additional studies should aim to validate this score and inspect clinical benefits of recollapse prophylaxis in patients at high risk.
Aims
To identify the mechanism in which way maltodextrin enhance bile tolerance in Lactobacillus plantarum Lp‐115.
Methods and Results
Based on determining the OD600 value and counting the numbers of ...viable cells by the pour plate method, the results showed that maltodextrin could not promote the strain growth directly, but could enhance the tolerance of bile in Lp‐115. The OD600 value of L. plantarum Lp‐115 cultured in MRSB broth with maltodextrin was three times higher than the control value. After supplementing the medium with 4·0% maltodextrin, the highest survival rate was observed when the bile concentration is 0.3%.
Conclusions
In summary, maltodextrin exhibited a significant improvement of bile tolerance and it could enhance cell hydrophobicity, shift the fatty acid composition of the membrane and induce the expression of a bile salt hydrolase gene (pva3) significantly.
Significance and Impact of the Study
This is the first report concerning the mechanism of maltodextrin enhancing the bile tolerance. This study promotes the application of maltodextrin as a choice to protect probiotic L. plantarum strains against the bile salt stress.
Oriental river prawn (Macrobrachium nipponense) has been widely cultured in Asian countries. However, its nutritional studies are very limited. In the present 8‐week study, we investigated the ...effects of dietary protein to energy ratio (P/E ratio) on the growth, feed utilization and body composition in juvenile M. nipponense (initial weight 0.302 ±0.03 g). Two‐factor experiment was designed and nine semi‐purified diets were formulated to contain three lipid levels (20, 80 and 140 g kg−1) and three protein levels (330, 380 and 430 g kg−1), producing P/E ratios from 16.5 to 23.4 mg KJ−1 protein. The results indicated that the growth, survival rate and protein efficiency were dose dependently improved by the increased dietary lipid, but not dietary protein content. Increased dietary lipid content and/or protein content increased lipid accumulation in whole body, hepatopancreas and muscle, but did not change the feed intake and hepatopancreas weight. In conclusion, our present study indicated that M. nipponense is a species with relatively high‐energy requirement. It could utilize dietary lipid content up to 140 g kg−1, while the dietary protein with more than 330 g kg−1 would not promote growth and protein efficiency. Taken together, 330 g kg−1 dietary protein and 140 g kg−1 dietary lipid level with P/E ratio 16.49 could be optimum for M. nipponense.
This meta‐analysis aimed to assess the gender‐specific differences in the relationship between circulating leptin levels and risk of type 2 diabetes. Published prospective studies that reported the ...association of leptin levels with risk of type 2 diabetes for a certain gender or those that reported gender‐specific associations were considered. Dose‐response relationships were assessed by the generalized least squares trend estimation and summary relative risks (RRs) with 95% confidence interval (CI) were computed with the random‐effects model. Stratified and sensitivity analyses were also performed to investigate potential sources of heterogeneity. Overall, 11 prospective studies were identified. The summary RR for an increment in leptin levels of 1‐log ng mL⁻¹ was 1.37 (95% CI, 1.13–1.66) for men and 0.96 (95% CI, 0.90–1.03) for women. The differences between genders were statistically significant (P for interaction = 0.006). Subgroup and sensitivity analyses generally confirmed the robustness of these findings. Furthermore, the increased risk in men appeared non‐linear, with a tendency to plateau at high levels (P for non‐linearity = 0.03). Little evidence of publication bias was found. Collectively, higher leptin levels were found to be associated with elevated risk of type 2 diabetes in men but not in women.
Quercetin (3,3′,4′,5,7-pentahydroxyflavone, Qu) is a promising cancer chemo-preventive agent for various cancers because it inhibits disease progression and promotes apoptotic cell death. In our ...previous study, we demonstrated that Qu could evoke ER stress to enhance drug cytotoxicity in ovarian cancer (OC). However, Qu-induced ER stress in OC is still poorly understood. Here, we demonstrated that Qu evoked ER stress to involve in mitochondria apoptosis pathway via the p-STAT3/Bcl-2 axis in OC cell lines and in primary OC cells. Unexpectedly, inhibition of ER stress did not reverse Qu-induced cell death. Further functional studies revealed that Qu-induced ER stress could activate protective autophagy concomitantly by activating the p-STAT3/Bcl-2 axis in this process. Moreover, the autophagy scavenger 3-MA was shown to enhance Qu’s anticancer effects in an ovarian cancer mice xenograft model. These findings revealed a novel role of ER stress as a “double edge sword” participating in Qu-induced apoptosis of OC and might provide a new angle to consider in clinical studies of biological modifiers that may circumvent drug resistance in patients by targeting protective autophagy pathways.
Graves’ disease (GD) is a complex autoimmune disorder in which genetic and environmental factors are both involved in the pathogenesis. Early‐onset patients have a shorter exposure time to ...environmental factors and are, therefore, good models to help understand the genetic architecture of GD. Based on previous studies of early‐onset GD, 11 single nucleotide polymorphisms (SNPs) and their related SNPs (R2 > .6), SNPs located within a ±1‐Mb region of the FOXP3 gene, and 20 validated GD‐risk SNPs were selected and screened for genotyping in 3735 GD and 4893 control patients to investigate whether early‐onset GD is a subtype of GD with distinct susceptibility genes. Ultimately, we did not confirm the reported genetic markers of early‐onset GD in our Chinese Han population but found that a GD‐risk SNP located in the human leukocyte antigen class I region—rs4947296—was more strongly correlated with early‐onset GD than non‐early‐onset GD. In addition, heterogeneity analysis of GD patients suggests that it may be more reasonable to define early‐onset GD as an onset age ≤20 years.
Spatially resolved transcriptomic technologies are promising tools to study complex biological processes such as mammalian embryogenesis. However, the imbalance between resolution, gene capture, and ...field of view of current methodologies precludes their systematic application to analyze relatively large and three-dimensional mid- and late-gestation embryos. Here, we combined DNA nanoball (DNB)-patterned arrays and in situ RNA capture to create spatial enhanced resolution omics-sequencing (Stereo-seq). We applied Stereo-seq to generate the mouse organogenesis spatiotemporal transcriptomic atlas (MOSTA), which maps with single-cell resolution and high sensitivity the kinetics and directionality of transcriptional variation during mouse organogenesis. We used this information to gain insight into the molecular basis of spatial cell heterogeneity and cell fate specification in developing tissues such as the dorsal midbrain. Our panoramic atlas will facilitate in-depth investigation of longstanding questions concerning normal and abnormal mammalian development.
Display omitted
•Stereo-seq enables large field-of-view spatial transcriptomics at cellular resolution•Stereo-seq reveals the spatial cell-type heterogeneity of mouse embryonic tissues•Stereo-seq maps the spatiotemporal transcriptomic dynamics during mouse organogenesis•Stereo-seq defines the spatiotemporal window of developmental disease vulnerability
Stereo-seq combines DNA nanoball-patterned arrays and tissue RNA capture to achieve large field-of-view spatial transcriptomics at cellular resolution, enabling the dissection of spatial cell-type heterogeneity of mouse embryonic tissues.
Aims
Paclitaxel is a type of broad‐spectrum anticancer drug in short supply. The price of acetyl‐CoA (17 709 677·4 USD mol−1), which is the acetyl group donor for the enzymatic synthesis of the ...intermediate, baccatin Ⅲ, is still the bottleneck of the mass production of paclitaxel. This study reports a novel acetyl group donor, which could substantially reduce the cost of production.
Methods and Results
In this study, a substrate spectrum with 14 kinds of representative acetyl‐donor substitutes predicted by computer‐aided methods was tested in a 10‐deacetylbaccatin Ⅲ‐10‐O‐acetyltransferase (DBAT) heterogeneous‐expressed open‐whole‐cell catalytic system. The results of computer prediction and experimental analysis revealed the rule of the acetyl‐donor compounds based on this substrate spectrum. N‐acetyl‐d‐glucosamine (30·95 USD mol−1, about 572 202‐fold cheaper than acetyl‐CoA) is selected as a suitable substitute under the rule. The yield when using N‐acetyl‐d‐glucosamine as acetyl donor in open‐whole‐cell catalytic system was 2·13‐fold of that when using acetyl‐CoA. In the in vivo system, the yield increased 24·17%, which may indicate its cooperation with acetyl‐CoA.
Conclusion
The success of open‐whole‐cell synthesis and in vivo synthesis of baccatin Ⅲ by adding N‐acetyl‐d‐glucosamine as acetyl substrate demonstrates that it is a useful substrate to improve the yield of baccatin Ⅲ.
Significance and Impact of the Study
All these findings provided a potential acetyl‐donor substitute for acetyl‐CoA, as well as a low cost and efficient method of preparing paclitaxel through baccatin Ⅲ semi‐synthesis.
Blood-circulating microRNAs (miRNAs) have been reported to be used as potential biomarkers in various cancers. MiR-101 has been found to act as a tumor suppressor in many tumor types, but little is ...known for osteosarcoma. The purpose of this study was to investigate miR-101 expression in osteosarcoma patients and assess its correlation with clinical features and prognosis. Serum samples from 152 osteosarcoma patients and 70 healthy controls were detected using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The data showed that miR-101 expression levels were remarkably underexpressed in serum samples from osteosarcoma patients compared to controls, and the post-treatment serum miR-101 expression was significantly higher than that in the pre-treatment expression. Low serum miR-101 expression was positively associated with advanced clinical stage and distant metastasis. Receiver operating characteristic (ROC) curve analysis showed that serum miR-101 could serve as a useful marker for osteosarcoma diagnosis, with a high sensitivity and specificity. Moreover, patients with high miR-101 expression had longer overall survival and recurrence free survival than those with low miR-101 expression. In addition, both univariate and multivariate analyses showed that serum miR-101 downregulation was associated with shorter overall survival and recurrence free survival. Our present results implicated serum miR-101 might be a useful biomarker for the clinical diagnosis and prognosis of osteosarcoma.
PDF
