Ultrasmall iron-quercetin metal natural product nanocomplex with antioxidant and macrophage regulation in rheumatoid arthritis

Oxidative stress, due to the disruption of the balance between reactive oxygen species (ROS) generation and the antioxidant defense system, plays an important role in the pathogenesis of rheumatoid arthritis (RA). Excessive ROS leads to the loss of biological molecules and cellular functions, release of many inflammatory mediators, stimulate the polarization of macrophages, and aggravate the inflammatory response, thus promoting osteoclasts and bone damage. Therefore, foreign antioxidants would effectively treat RA. Herein, ultrasmall iron-quercetin natural coordination nanoparticles (Fe-Qur NCNs) with excellent anti-inflammatory and antioxidant properties were constructed to effectively treat RA. Fe-Qur NCNs obtained by simple mixing retain the inherent ability to remove ROS of quercetin and have a better water-solubility and biocompatibility. In vitro experiments showed that Fe-Qur NCNs could effectively remove excess ROS, avoid cell apoptosis, and inhibit the polarization of inflammatory macrophages by reducing the activation of the nuclear factor-κ-gene binding (NF-κB) pathways. In vivo experiments showed that the swollen joints of mice with rheumatoid arthritis treated with Fe-Qur NCNs significantly improved, with Fe-Qur NCNs largely reducing inflammatory cell infiltration, increasing anti-inflammatory macrophage phenotypes, and thus inhibiting osteoclasts, which led to bone erosion. This study demonstrated that the new metal-natural coordination nanoparticles could be an effective therapeutic agent for the prevention of RA and other diseases associated with oxidative stress.

Correlation between TyG and TyG combined obesity index and prehypertension in middle-aged and elderly population / 公共卫生与预防医学

Objective To explore the correlation between Triglyceride Glucose Index (TyG) and its combined obesity Index and prehypertension in middle-aged and elderly population in China, and to provide a monitoring tool for better hierarchical management of prehypertension population. Methods A total of 5 099 people with non-hypertension were enrolled through the database of the China Health and Retirement Longitudinal Study (CHARLS). Body mass index (BMI), waist circumference (WC) and waist to height ratio (WTHR) were obtained, and TyG-BMI, TyG-WC and TyG-WTHR indexes were calculated by multiplying the TyG index with the three indexes respectively. Logistic regression analysis was used to explore the relationship between TyG index and obesity index and prehypertension. The DeLong method was used to compare the values of Area Under the Curve (AUC) of each index to distinguish their value in identifying prehypertension. Results Compared with the normal blood pressure group, the prehypertension group was older, and the blood pressure was higher. Logistic regression analysis showed that higher levels of TyG-BMI and TyG-WC index were significantly associated with prehypertension. Compared with the lowest quartile array Q1, the OR values of TyG-BMI Q2-Q4 were 1.24 (95%CI :1.03-1.49), 1.40 (95%CI :1.10-1.76) and 1.91 (95%CI :1.43-2.56), while the OR values of TyG-WC index Q2-Q4 group were 1.45 (95%CI :1.19-1.75), 1.49 (95%CI :1.13-1.95), and 2.12 (95%CI: 1.47-3.07), respectively. There was no statistically significant difference in the AUC value between TyG-WC and TyG-BMI (P =0.0998). Conclusion Among the four novel indexes, higher levels of TyG-WC and TyG-BMI are positively correlated with prehypertension. Compared with TyG and TyG-WTHR, TyG-WC and TyG-BMI have the potential to become an effective auxiliary means in the individual hierarchical management of prehypertension in the middle-aged and elderly.

Accurately Differentiating COVID-19, Other Viral Infection, and Healthy Individuals Using Multimodal Features via Late Fusion Learning

Effectively identifying COVID-19 patients using non-PCR clinical data is critical for the optimal clinical outcomes. Currently, there is a lack of comprehensive understanding of various biomedical features and appropriate technical approaches to accurately detecting COVID-19 patients. In this study, we recruited 214 confirmed COVID-19 patients in non-severe (NS) and 148 in severe (S) clinical type, 198 non-infected healthy (H) participants and 129 non-COVID viral pneumonia (V) patients. The participants clinical information (23 features), lab testing results (10 features), and thoracic CT scans upon admission were acquired as three input feature modalities. To enable late fusion of multimodality data, we developed a deep learning model to extract a 10-feature high-level representation of the CT scans. Exploratory analyses showed substantial differences of all features among the four classes. Three machine learning models (k-nearest neighbor kNN, random forest RF, and support vector machine SVM) were developed based on the 43 features combined from all three modalities to differentiate four classes (NS, S, V, and H) at once. All three models had high accuracy to differentiate the overall four classes (95.4%-97.7%) and each individual class (90.6%-99.9%). Multimodal features provided substantial performance gain from using any single feature modality. Compared to existing binary classification benchmarks often focusing on single feature modality, this study provided a novel and effective breakthrough for clinical applications. Findings and the analytical workflow can be used as clinical decision support for current COVID-19 and other clinical applications with high-dimensional multimodal biomedical features. One sentence summaryWe trained and validated late fusion deep learning-machine learning models to predict non-severe COVID-19, severe COVID-19, non-COVID viral infection, and healthy classes from clinical, lab testing, and CT scan features extracted from convolutional neural network and achieved predictive accuracy of > 96% to differentiate all four classes at once based on a large dataset of 689 participants.

Serum vitamin D nutritional status of 0-6 years old children in Suzhou area / 国际检验医学杂志

Objective To study the level of serum 25 (OH) D3in children in suzhou area, and to provide scientific basis for the rational supplement of vitamin D for children aged 0-6years.Methods From September2015to September 2016, 15 010children underwent routine physical examination in the Children′s Health Clinic of Suzhou Municipal Hospital were selected, of whom 7 905were male and 7 105were female.The serum 25 (OH) D3was detected by collecting their fingerling blood.Results (1) The mean serum 25 (OH) D3of15 010children aged 0to 6in Suzhou was (35.83±13.23) μg/L, and the mean serum 25 (OH) D3of male and female were (36.48±13.25) and (35.11±13.16) μg/L respectively, and the differences were statistically significant (P＜0.01). (2) The mean level of serum 25 (OH) D3of 0-＜3, 3-＜6, 6-＜12, 12-＜36, 36-＜48and≥48months old children were (34.49±11.53), (41.15±13.86), (48.03±17.25), (46.12±17.69), (28.49±16.55) and (42.28±17.59) μg/L.The detection levels of serum 25 (OH) D3between the age groups were statistically significant (P＜0.05) except the children 3-＜6months and≥48months. (3) From January to December, the detection levels of serum 25 (OH) D3 were statistically significant between different months (P＜0.01) except in January, February, March and November, as well as July and August.The serum25 (OH) D3in each month was graded according to the vitamin D level, and the detection levels of serum 25 (OH) D3between different months were statistically significant (P＜0.01).The proportion of serum 25 (OH) D3over 30μg/L was less than 50％in January, March and November.The ratio ranged from 50％to 60％in February, June and December.The ratio ranged from 60％to 70％in the July, August and September, while the proportion was over 70％in April, May and October.Conclusion The level of serum 25 (OH) D3in children in Suzhou area was decreased obviously, and health education should be strengthened, and attention should be paid to intaking of vitamin D in children.

Loss of long noncoding RNA FOXF1-AS1 regulates epithelial-mesenchymal transition, stemness and metastasis of non-small cell lung cancer cells.

Although recent evidence shows that long noncoding RNAs (lncRNAs) are involved in the regulation of gene expression and cancer progression, the understanding of the role of lncRNAs in lung cancer metastasis is still limited. To identify novel lncRNAs in non-small cell lung cancer (NSCLC), we profile NSCLC tumor and matched normal samples using GeneChip® Human Gene 2.0 ST Array, which provides the most accurate, sensitive, and comprehensive measurement of protein coding and lncRNA transcripts. We identified a panel of key factors dysregulated in lung cancer. Among them, the expression of FOXF1-AS1 was significantly downregulated in lung cancer. Stable overexpression of FOXF1-AS1 inhibits lung cancer cell migration and invasion by regulating EMT. Meanwhile, loss of FOXF1-AS1 mediates stem-like properties of lung cancer cells. Interestingly, we found that FOXF1-AS1 physically associates with PRC2 components EZH2 and loss of FOXF1-AS1 mediates cell migration and stem-like properties require EZH2. Loss of FOXF1-AS1 is also correlated with downregulation of FOXF1 in lung cancer. These results suggested that FOXF1-AS1 might regulate EMT, stemness and metastasis of NSCLC cells via EZH2, indicating it as a therapeutic target for future treatment of NSCLC.

Toxic effects of mixture of volatile organic compounds on mice testis related enzymes and hormones / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To evaluate the toxic effects of mixture of volatile organic compounds (VOCs) on Mice Testis related enzymes and hormones.</p><p><b>METHODS</b>After determining the median lethal dose (LD₅₀) of VOCs using the acute toxicity test, 40 male clean inbred Kunming mice were assigned to 1/8 LD₅₀ VOCs exposure group, 1/4 LD₅₀ VOCs exposure group, and 1/2 LD₅₀ VOCs exposure group, as well as positive control group with cyclophosphamide (60 mg/kg) and negative control group with tea oil, with 8 mice in each group. The mice were intraperitoneally injected with respective agents for 5 days. The levels of testis testosterone, estradiol, follicle stimulating hormone, and luteinizing hormone were determined by ELISA. Meanwhile, the activity of testicular marked enzymes such as lactate dehydrogenase, gamma-glutamyl transpeptidase, acid phosphatase, and glucose-6-phosphate dehydrogenase were examined.</p><p><b>RESULTS</b>Compared with the negative control group, the 1/8 LD₅₀ exposure group had a significantly increased testis coefficient (P<0.05). Both the activity of testicular marked enzymes and the levels of testicular sex hormones in all exposure groups showed significant downward trends with increasing VOC doses compared with those in the negative control group (P<0.05).</p><p><b>CONCLUSION</b>VOCs have obvious toxicity to mouse testis by changing the levels of testicular sex hormones and the activity of testicular marked enzymes.</p>

Gene expression in liver injury caused by long-term exposure to titanium dioxide nanoparticles in mice.

Although liver toxicity induced by titanium dioxide nanoparticles (TiO(2) NPs) has been demonstrated, very little is known about the molecular mechanisms of multiple genes working together underlying this type of liver injury in mice. In this study, we used the whole-genome microarray analysis technique to determine the gene expression profile in the livers of mice exposed to 10 mg/kg body weight TiO(2) NPs for 90 days. The findings showed that long-term exposure to TiO(2) NPs resulted in obvious titanium accumulation in the liver and TiO(2) NP aggregation in hepatocyte nuclei, an inflammatory response, hepatocyte apoptosis, and liver dysfunction. Furthermore, microarray data showed striking changes in the expression of 785 genes related to the immune/inflammatory response, apoptosis, oxidative stress, the metabolic process, response to stress, cell cycle, ion transport, signal transduction, cell proliferation, cytoskeleton, and cell differentiation in TiO(2) NP-exposed livers. In particular, a significant reduction in complement factor D (Cfd) expression following long-term exposure to TiO(2) NPs resulted in autoimmune and inflammatory disease states in mice. Therefore, Cfd may be a potential biomarker of liver toxicity caused by TiO(2) NPs exposure.

A preliminary study on the influence of low-iron environment on serum osteocalcin and bone micro-structure in ovariectomized mice / 中华内分泌代谢杂志

Objective To investigate the changes of serum osteocalcin and bone micro-structure in ovariectomized mice exposed to low-iron environment.Methods Twenty-four 12-week-old female C57BL/6 mice were divided equally into sham operation (SHAM) group,model(OVX) group,and low iron(OVX+DFO) group.In low-iron group,deferoxamine(DFO) was injected 3 times per week for 5 weeks after operation ; the other groups were injected with the same dose of 0.9％ normal saline for 5 weeks.The serum,left femur,uterus were harvested after five weeks of treatment.The serum osteocalcin and ferritin levels were measured by ELISA kit,the weight of the uterus was recorded by analytical balance.A high resolution micro-CT was used to scan the left femur for cortical bone and cancellous bone analysis.Results (1) The serum osteocalcin and serum ferritin levels in low-iron group were significantly lower than those in the other 2 groups (P＜0.01) ; (2) Compared with the sham group and ovx group,there were significant decrease of the BMD、BV/TV and Tb.N,but increase of Tb.Th and Tb.Sp in low-iron group (P＜0.01).Conclusion A certain dose of DFO (30 mg/kg) can decrease the serum ferritin levels as well as the bone formation index in ovariectomized mice.

Protective effects of parathyroid hormone on radiation-induced hematopoietic damage in mice / 中华放射医学与防护杂志

Objective To study the protective effects of parathyroid hormone (PTH) on radiationinduced hematopoietic damage in mice.Methods A total of sixty male C57 mice were irradiated by 60Co γ-rays to induce hematopoietic injuries,and then the mice were randomly divided into PTH and control group.The PTH-treated group was treated with PTH ( 80 μg· kg- 1 · d - 1 ) intraperitoneally everyday.The control group was given equivalent volume saline.Peripheral blood cell number,bone marrow mononuclear cell number,granulocyte-macrophage colony forming units ( CFU-GM ) and CD34 positive cells in bone marrow were detected.Results With the whole post-irradiation period,the WBC and bone marrow mononuclear cell numbers in PTH-treated mice were significantly higher than those in saline-treated mice (t=6.32,9.19,11.18,7.44 and 4.42,P ＜ 0.05).The RBC numbers in PTH-treated mice were significantly higher than those in control mice at 10 d,15 d and 20 d post-irradiation (t =6.48,3.66 and 4.98,P ＜0.05 ).The PLT numbers in PTH-treated mice were significantly higher than those in control group at 5 and 30 d post-irradiation ( t =2.57 and 3.10,P ＜ 0.05 ).PTH increased CD34 positive cell and CFU-GM numbers in bone marrow after irradiation ( t =16.12,7.82 and 20.00,P ＜ 0.05 ).Conclusions PTH could improve the hematopoietic recovery after irradiation.

Relationship between single nucleotide polymorphism of the equilibrative nucleoside transporter ENT3 and susceptibility to lung cancer / 中国肺癌杂志

<p><b>BACKGROUND AND OBJECTIVE</b>The transport of nucleoside transmembrane mediated by equilibrative nucleoside transporter (ENT) plays an important role in regulating various cellular functions, and the ENT gene may be candidate gene of tumors. The aim of this study is to investigate the association between the single nudcleotide polymorphism (SNP) of ENT3 and the hereditary susceptibility of lung cancer.</p><p><b>METHODS</b>A case-control study was performed involved in 351 lung cancer patients and 207 cancer-free controls from Chinese population in Shanghai pulmonary hospital. The rs10999776 (C>T) polymorphism was determined by using Real-time PCR with AllGlo probes. The frequency distribution of genotypes and allele between lung cancer and controls groups was analyzed by chi-square test. The association between polymorphism in the ENT3 gene with the risk of lung cancer was estimated by computing odds ration (OR) and 95%CI.</p><p><b>RESULTS</b>The genotype (CC, TC, IT) and allele distribution of the ENT3 SNP in the patients with lung cancer was not significantly different compared with that in controls (P > 0.05). Compared with never-smokers with wild homozygous genotype, smokers with T allele (TC+TT) had increased risk of lung cancer (OR = 2.848, 95% CI: 1.536-4.879, P = 0.005), and those with pack-years of smoking more than 30 had higher risk (OR = 3.076, 95% CI: 2.308-6.741, P = 0.001). And the risk of squamous cell carcinoma significantly increased in smokers, especially those with T allele (TC+TI) genotype (OR = 6.066, 95% CI: 2.884-12.758, P < 0.001). The genotype with smoking conditions had no significant effect on adenocarcinoma (all P > 0.05).</p><p><b>CONCLUSION</b>The results suggested rs10999776 polymorphism may implicate in the risk of squamous cell carcinoma in Chinese population which may interact with smoking-exposure.</p>

EFFECT OF 1,25-DIHYDROXYVITAMIN D_3 ON THE PROCESS OF PHAGOCYTIZING STAPHYLOCOCCUS AUREUS IN MACROPHAGES / 营养学报

Objective To investigate the effect of vitamin D (VD) on macrophage to phagocytize Staphylococcus aureus (SA). Method Macrophoge cell lines RAW264.7 were allocated into 3 groups:control group(C),bacterium group(B),active vitamin D+ bacterium group (VD+B). Cells in the VD+B group were incubated with 10-8mol/L active vitamin D for 24h,then cells in the VD+B group and the B group were cultured with SA for 1h,and phagocytosis rate,mitochondrial membrane potential,[Ca～(2+)]i,reactive oxygen species were determined by flow cytometry (FCM). Results The phagocytizing activity of macrophage in VD+B group was significantly higher than that in B group 1h after infection,At the same time,the mitochondrial member potential and [Ca～(2+)]i of macrophage in VD+B group were distinctly lower than that in B group; but reactive oxygen species of macrophage in the VD+B group was insignificantly different from B group. Conclusion Vitamin D can reinforce the phagocytizing activity of macrophage and inhibit the apoptosis of macrophage after phagocytize Staphylococrcus aureus.