Publications by authors named "Yu W"

10,619 Publications

Silent information regulator 1 suppresses epithelial-to-mesenchymal transition in lung cancer cells via its regulation of mitochondria status.

Life Sci 2021 Jun 10;280:119716. Epub 2021 Jun 10.

Department of Toxicology, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Shaanxi Key Lab of Free Radical Biology and Medicine, School of Public Health, Fourth Military Medical University, Xi'an 710032, China. Electronic address:

Aims: Silent information regulator 1 (SIRT1) is a NAD-dependent protein-modifying enzyme involved in regulating gene expression, DNA damage repair, cell metabolism, and mitochondrial functions. Given that it acts as both a tumor promoter and suppressor, the complex mechanisms underlying SIRT1 signaling in cancer remain controversial. Epithelial-to-mesenchymal transition (EMT) plays a key role in the progression of carcinogenesis and tumors metastasis. Studies have shown that mitochondrial defects are critical in EMT process, and SIRT1 is found to regulate the generation and energy metabolism of mitochondria. Here, we elucidate a novel mechanism by which SIRT1 affects EMT in lung cancer cells via its regulation on mitochondria.

Main Methods: SIRT1 signaling was detected in TGF-β1-induced EMT and was found to regulate mitochondria status, including mitochondrial biogenesis-related protein levels as detected by western blotting, mitochondrial structure observed by transmission electron microscopy, and respiratory functions analyzed by a respiration capacity assay. The effects of modulating SIRT1 expression on EMT and migration of lung cancer cells or normal cells were evaluated by in vitro and in vivo models.

Key Findings: We found that the regulation of SIRT1 signaling on the biogenesis or functions of mitochondria was critical to EMT. Overexpression of SIRT1 reduced EMT or metastasis potential of lung cancer cells by improving the quantity and quality of mitochondria, whereas silencing SIRT1 promote EMT in cancer cells, even in normal cells by disturbing mitochondria status.

Significance: Consequently, SIRT1 is an attractive therapeutic target for reversing EMT or tumor metastasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lfs.2021.119716DOI Listing
June 2021

Multi-functional carboxymethyl chitin-based nanoparticles for modulation of tumor-associated macrophage polarity.

Carbohydr Polym 2021 Sep 24;267:118245. Epub 2021 May 24.

Key Laboratory of Coal Conversion and New Carbon Materials of Hubei Province, School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan, Hubei 430081, China; State Key Laboratory of Separation Membranes and Membrane Process, School and Chemical Engineering & School of Environmental Science and Engineering, Tiangong University, Tianjin 300378, China; College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, Hubei 430072, China. Electronic address:

Current challenge of using cytokines is its poor distribution and systemic side effects. To avoid this issue, we prepared the tumor-targeted and microenvironment-responsive nanocarriers (TRN), which were consisted of α-tocopheryl succinate (α-TOS) loaded mesoporous silica nanoparticles as cores, and surface-modified by thioketal-linkage, electrostatically coated with carboxymethyl chitin, and further anchored glucose-regulated protein 78-binding peptide as shells for encapsulating IL-12. TRN showed a size of 260 nm after encapsulated IL-12 and α-TOS with loading content of 0.0206% and 7.21%, respectively, and exhibited good biocompatibility to 4 T1 cells and macrophages. Moreover, IL-12/α-TOS loaded TRN displayed obvious anti-tumor efficacy on BALB/c nude mice bearing 4 T1 tumors, which was derived from promoted targeting to tumor tissue, endocytosed by macrophages and locally release IL-12 to subsequently repolarize tumor-associated macrophages into tumoricidal M1 phenotype with reduced side effects. The nanosystem exhibited as a promising strategy with functional conversion of macrophages in tumor microenvironment for anti-tumor therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.carbpol.2021.118245DOI Listing
September 2021

Novel photosensitive dual-anisotropic conductive Janus film endued with magnetic-luminescent properties and derivative 3D structures.

J Colloid Interface Sci 2021 May 26;601:899-914. Epub 2021 May 26.

Key Laboratory of Applied Chemistry and Nanotechnology at Universities of Jilin Province, Changchun University of Science and Technology, Changchun 130022, China.

A new photosensitive dual-anisotropic conductive Janus film (PDCJF) is proposed for the first time. It is rationally designed and manufactured by facile electrospinning. PDCJF is firstly constructed using 2,7-dibromo-9-fluorenone (DBF) with photoconductive and luminescent properties. Janus nanofibers are respectively used as the building units to construct the top layer (T-PDCJF) and the bottom layer (B-PDCJF) of PDCJF. The two layers are tightly bonded to form PDCJF. Under light irradiation, there is photosensitive dual-anisotropic conduction in PDCJF, but there is no anisotropic conduction without light. Thus, the transition of PDCJF from mono-functional magnetism to tri-functionalities is realized under light and without light. The luminescence color of PDCJF is tunable and it emits white-light. This is made possible by modulating the amounts of luminescent substances and excitation wavelength. The microscopic Janus nanofibers used as building units and macroscopic Janus film structure ensure high photosensitive dual-anisotropic conduction and excellent fluorescence in PDCJF. The two-dimensional (2D) PDCJF is rolled to obtain three-dimensional (3D) Janus-type tubes and 2D plus 3D complete flag-like structures with exceptional multi-functionalities. The new findings can strongly guide in developing advanced multi-functional nanostructures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcis.2021.05.141DOI Listing
May 2021

A synthetic peptide AWRK6 ameliorates metabolic associated fatty liver disease: involvement of lipid and glucose homeostasis.

Peptides 2021 Jun 10;143:170597. Epub 2021 Jun 10.

Department of Stem Cells and Regenerative Medicine, Key Laboratory of Cell Biology, National Health Commission of China, And Key Laboratory of Medical Cell Biology, Ministry of Education of China, China Medical University, Shenyang, 110122, China. Electronic address:

Metabolic associated fatty liver disease (MAFLD) is the leading common chronic liver disease affecting more than one-quarter of the population worldwide, but no pharmacological therapy was approved specifically. A synthetic peptide AWRK6 developed in our group based on the antimicrobial peptide Dybowskin-2CDYa was found to attenuated diabetes as a novel GLP-1 receptor agonist candidate. The effects of AWRK6 on MAFLD and its underlying mechanisms were investigated in this paper. In high energy diet (HED)-induced MAFLD mice, obesity and hepatic steatosis were alleviated by AWRK6 via intraperitoneal injection. The biochemistry measurements data indicated that the abnormal lipid metabolism was relieved and the glucose metabolism was improved significantly. Further, the phosphorylation of liver PI3K/AKT/AMPK/ACC was elevated significantly by AWRK6 treatment. Moreover, the effects of AWRK6 on lipid accumulation and insulin sensitivity in human cells were verified using oleic acid-induced HepG2 fatty liver cell model and insulin-induced HepG2 cells, respectively. These in vitro and in vivo results demonstrated that the peptide AWRK6 ameliorates MAFLD by improving lipid and glucose metabolism homeostasis, and it is mediated by the PI3K/AKT/AMPK/ACC signaling pathway. Thus, AWRK6 has a potential in preventing MAFLD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.peptides.2021.170597DOI Listing
June 2021

Conjugation of haloalkane dehalogenase DhaA with arabinogalactan to increase its stability.

J Biotechnol 2021 Jul 9;335:47-54. Epub 2021 Jun 9.

State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, China. Electronic address:

Haloalkane dehalogenase DhaA can catalyze the hydrolytic cleavage of carbonhalogen bonds, along with production of the corresponding alcohol, a proton and a halide. However, DhaA suffers from poor environmental tolerance, such as sensitivity to high temperature, low pH and hypersaline. Arabinogalactan (AG) is a hydrophilic polysaccharide with highly branched long chains. DhaA was conjugated with AG to improve the environmental stability of DhaA in the present study. Each DhaA was averagely conjugated with 4∼5 AG molecules. Conjugation of AG essentially maintained the enzymatic activity of DhaA (91.4 %) without apparent structural alteration. The hydration layer formed by AG could reduce the solvent accessible area of DhaA and slow the protonation process, thereby improving the pH and high salt stability of DhaA. In particular, the remaining activities of the conjugate (AG-DhaA) were 35.3 % after treatment at pH4.0 for 1 h, and 80.8 % in 1 M NaCl after treatment for 16 h. As compared with DhaA, AG-DhaA showed slightly different kinetic parameters (K M of 1.90 μmol/L and k cat of 2.60 s -1).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbiotec.2021.06.002DOI Listing
July 2021

Migration and abiotic transformation of estrone (E1) and estrone-3-sulfate (E1-3S) during soil column transport.

Environ Geochem Health 2021 Jun 12. Epub 2021 Jun 12.

Key Laboratory of Hydraulic and Waterway Engineering of the Ministry of Education, School of River and Ocean Engineering, Chongqing Jiaotong University, Chongqing, 400074, China.

Steroid estrogens have received worldwide attention and given rise to great challenges of aquatic ecosystems security, posing potential adverse effects on aquatic organisms and human health even at low levels (ng/L). The present study focused on understanding the mobility and abiotic transformation of estrone (E1) and estrone-3-sulfate (E1-3S) over spatial and time scales during soil transport. Column transport experiments showed that the migration capacity of E1-3S was far stronger than E1 in soil. The calculated groundwater ubiquity score and leachability index values also indicated the high leaching mobility of E1-3S. The hydrolysis of E1-3S and abiotic transformation into estradiol and estriol was observed in the sterilized soil. Furthermore, possible transformation products (e.g., SE, E2, E1 dimer, E1-E2 dimer) of E1 and E1-3S in soil were analyzed and identified after the column transport experiments. The estrogenic activity was estimated by 17β-estradiol equivalency values during the transport process in aqueous and soil phases. Additionally, the potential leaching transport to groundwater of E1-3S requires further critical concern.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10653-021-00968-1DOI Listing
June 2021

Complete genome analysis of the newly isolated Shigella sonnei phage vB_SsoM_Z31.

Arch Virol 2021 Jun 11. Epub 2021 Jun 11.

Dalian SEM Bio-Engineering Technology Co. Ltd, Dalian, 116620, China.

This work describes the characterization and genome annotation of the newly isolated lytic phage vB_SsoM_Z31 (referred to as Z31), isolated from wastewater samples collected in Dalian, China. Transmission electron microscopy revealed that phage Z31 belongs to the family Myoviridae, order Caudovirales. This phage specifically infects Shigella sonnei, Shigella dysenteriae, and Escherichia coli. The genome of the phage Z31 is an 89,355-bp-long dsDNA molecule with a G+C content of 38.87%. It was predicted to contain 133 ORFs and encode 24 tRNAs. No homologs of virulence factor genes or antimicrobial resistance genes were found in this phage. Based on the results of nucleotide sequence alignment and phylogenetic analysis, phage Z31 was assigned to the genus Felixounavirus, subfamily Ounavirinae.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00705-021-05121-yDOI Listing
June 2021

Monte Carlo determination of dose coefficients at different developmental stages of zebrafish (Danio rerio) in experimental condition.

J Environ Radioact 2021 Jun 8;237:106667. Epub 2021 Jun 8.

State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou, 215123, China; Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions. Electronic address:

The release of liquid effluent of nuclear power into aquatic system increases with the rapid development of nuclear facilities in coastal and inland regions. Aquatic model animals are very important for the study of the radiation hazards to non-human biota in water environment and its extrapolation of dose-effect relationship to human models. However, the study of the radiation dose rate calculation model of the aquatic animal zebrafish is still on the homogeneous isotropic model used for the protection of the environment. A series of zebrafish models (including adults, larvae and embryos, named zebrafish-family: ZF-family) with multiple internal organs are established in this study to investigate the mechanism of radiation damage effect in order to protect non-human species. The internal and external dose coefficients (DCs) of the whole body, heart and gonads of zebrafishes are calculated in water environment with the combination of the real experimental culture condition, using Monte Carlo application package GATE (Geant4 Application for Emission Tomography) and eight nuclides, i.e., H, C, Sr, Co, Ag, Cs, Cs, I, which are commonly found in the liquid effluent of nuclear power plants, as the source items, The results show that the level of nuclide γ energy determines the external DCs (DC), and Sr plays the most important role in internal DCs (DC). The comparison between the external DCs of the heart and gonad and that of the whole body shows that DCs (DC) of heart and gonad for females are 80% and 43% lower than that of whole body, respectively, while for males, the DCs (DC) of heart is 44% lower than that of the whole body, and DCs (DC) of gonad is slightly higher than that of the whole body for most nuclides (up to 25%).The dose of internal radiation makes greater contribution than that of external radiation to pure beta emitter (H, C, Sr). This internal DCs of ZF-family model with complex internal structure turns out to demonstrate more sensitive DCs change trend and higher calculation values compared with the internal DCs of the simple ellipsoid model. In this model, the photon emitter with strong penetrating power has higher internal DCs, while the low-energy pure beta nuclide does not alter much. In conclusion, it is vital to carry out refined systematic modeling for model organisms, and the determination of DCs of model organs can promote the evaluation of the radiation effects on non-human species.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jenvrad.2021.106667DOI Listing
June 2021

Flower-like Spherical α-Ni(OH) Derived NiP as Superior Anode Material of Sodium-Ion Batteries.

Chem Asian J 2021 Jun 11. Epub 2021 Jun 11.

New Energy Research Institute, School of Environment and Energy, South China University of Technology Guangzhou Higher Education Mega Centre, Guangzhou, 510006, P. R. China.

Transition metal phosphides (TMPs) are promising anode candidates for sodium-ion batteries, due to their high theoretical specific capacity and working potential. However, the low conductivity and excessive volume variation of TMPs during insertion/extraction of sodium ions result in a poor rate performance and long-term cycling stability, largely limiting their practical application. In this paper, NiP nanoparticles encapsulated in three-dimensional graphene (NiP @rGO) were obtained from the flower-like spherical α-Ni(OH) by phosphating and carbon encapsulation processes. When used as a sodium-ion batteries anode material, the NiP @rGO composite shows an excellent cycling performance (117 mA h g at 10 A g after 8000 cycles). The outstanding electrochemical performance of NiP @rGO is ascribed to the synergistic effect of the rGO and NiP . The rGO wrapped on the NiP nanoparticles build a conductive way, improving ionic and electronic conductivity. The effective combination of NiP nanoparticles with graphene greatly reduces the aggregation and pulverization of NiP nanoparticles during the discharge/charge process. This study may shed light on the construction of high-performance anode materials for sodium-ion batteries and to other electrode materials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/asia.202100387DOI Listing
June 2021

Application of first-order kinetics modeling to reveal the nature of starch digestion characteristics.

Food Funct 2021 Jun 11. Epub 2021 Jun 11.

School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China. and Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Institutes of Agricultural Science and Technology Development of Yangzhou University, Yangzhou 225009, Jiangsu, China.

Mathematical modeling of in vitro starch digestograms is essential to understand starch structure-digestibility relationships as it covers all detailed information of the starch digestograms with only a few kinetics-based parameters. However, many assumptions exist for these mathematical models, which are frequently overlooked by researchers and lead to inappropriate or even wrong interpretations of the fitted parameters. This review presents a critical evaluation of four mostly applied empirical first-order kinetics models including single first-order kinetics (SK), logarithm of slope (LOS) transformed kinetics, parallel first-order kinetics (PK) and the combination of parallel and sequential (CPS) kinetics models. For homogeneous food systems, the SK model is perfectly suitable, whereas the LOS, PK and CPS models were suitably developed for food systems containing multiple digestible fractions. For the digestion of starch containing multiple digestible fractions, the LOS model assumed a sequential digestion pattern, whereas the PK model assumed a parallel pattern. In the current review, there is also emphasis on the recently developed CPS model, which is able to differentiate the sequential and parallel digestion patterns for different starch digestible fractions existing in food systems. Understanding these assumptions enables a better selection of an appropriate mathematical model for improving the understanding of in vitro starch digestion characteristics. This review meets the growing interest of the food industry in terms of developing a new generation of foods with slower starch digestibility.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1fo00450fDOI Listing
June 2021

Appropriate use of antimicrobial therapy for COVID-19 co-infection.

Immunotherapy 2021 Jun 11. Epub 2021 Jun 11.

Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/imt-2021-0134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202506PMC
June 2021

Puerarin reduces impairment of intestinal and adipose immune responses to influenza virus infection in mice.

Arch Virol 2021 Jun 10. Epub 2021 Jun 10.

Basic Medical College, Guangzhou University of Chinese Medicine, 12 Jichang Rd., San Yuanli St., Bai Yun Dist., Guangzhou, 510405, Guangdong, People's Republic of China.

Influenza is an acute viral respiratory disease that can also cause gastroenteritis-like symptoms, such as abdominal pain, nausea, vomiting, and diarrhea. Immune dysfunction of adipose tissue is involved in the occurrence and prognosis of influenza viral pneumonia. In this study, we analyzed intestinal and adipose immune responses in mice infected with influenza virus and found that the impairment of intestinal and adipose immunity to influenza virus infection could be reversed by treatment with puerarin, a medicinal compound isolated from Pueraria lobata (called "gegen" in Chinese). We found that the lungs, small intestines (duodenum, ileum, jejunum) and large intestines (colon and rectum) of infected mice showed obvious inflammatory lesions, with significantly increased levels of virus, inflammatory cytokines (interleukin [IL]-6, IL-17, and tumor necrosis factor-α), Toll-like receptors 3, 4, and 9, and integrin αvβ3 and α4, and a decreased level of secreted IgA compared to the normal control group (NC) (P < 0.05-0.001). Influenza virus infected mesenteric lymph nodes and adipose tissue, and adipokines (leptin, visfatin, "chemerin", and adiponectin) of lung and mesenteric adipose tissue were dysregulated. Puerarin treatment reversed the impairment of the intestinal and adipose immune responses in mice infected with influenza virus. Our findings suggest that influenza virus can infect adipose tissue and lead to intestinal adipose immune dysfunction in normal-weight mice and that the impairment of the intestinal and adipose immune response to influenza virus infection can be reversed by puerarin treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00705-021-05112-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191723PMC
June 2021

A framework for automated gene selection in genomic applications.

Genet Med 2021 Jun 10. Epub 2021 Jun 10.

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, Cambridge, MA, USA.

Purpose: An efficient framework to identify disease-associated genes is needed to evaluate genomic data for both individuals with an unknown disease etiology and those undergoing genomic screening. Here, we propose a framework for gene selection used in genomic analyses, including applications limited to genes with strong or established evidence levels and applications including genes with less or emerging evidence of disease association.

Methods: We extracted genes with evidence for gene-disease association from the Human Gene Mutation Database, OMIM, and ClinVar to build a comprehensive gene list of 6,145 genes. Next, we applied stringent filters in conjunction with computationally curated evidence (DisGeNET) to create a restrictive list limited to 3,929 genes with stronger disease associations.

Results: When compared to manual gene curation efforts, including the Clinical Genome Resource, genes with strong or definitive disease associations are included in both gene lists at high percentages, while genes with limited evidence are largely removed. We further confirmed the utility of this approach in identifying pathogenic and likely pathogenic variants in 45 genomes.

Conclusion: Our approach efficiently creates highly sensitive gene lists for genomic applications, while remaining dynamic and updatable, enabling time savings in genomic applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41436-021-01213-xDOI Listing
June 2021

Hybrid AI-assistive diagnostic model permits rapid TBS classification of cervical liquid-based thin-layer cell smears.

Nat Commun 2021 06 10;12(1):3541. Epub 2021 Jun 10.

Department of Pathology, Guangdong Provincial Women's and Children's Dispensary, Shenzhen, Guangdong Province, PR China.

Technical advancements significantly improve earlier diagnosis of cervical cancer, but accurate diagnosis is still difficult due to various factors. We develop an artificial intelligence assistive diagnostic solution, AIATBS, to improve cervical liquid-based thin-layer cell smear diagnosis according to clinical TBS criteria. We train AIATBS with >81,000 retrospective samples. It integrates YOLOv3 for target detection, Xception and Patch-based models to boost target classification, and U-net for nucleus segmentation. We integrate XGBoost and a logical decision tree with these models to optimize the parameters given by the learning process, and we develop a complete cervical liquid-based cytology smear TBS diagnostic system which also includes a quality control solution. We validate the optimized system with >34,000 multicenter prospective samples and achieve better sensitivity compared to senior cytologists, yet retain high specificity while achieving a speed of <180s/slide. Our system is adaptive to sample preparation using different standards, staining protocols and scanners.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-23913-3DOI Listing
June 2021

A potential antiviral activity of Esculentoside A against binding interactions of SARS-COV-2 spike protein and angiotensin converting enzyme 2 (ACE2).

Int J Biol Macromol 2021 Jun 7;183:2248-2261. Epub 2021 Jun 7.

Institute of Tropical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, PR China. Electronic address:

The recent emergence of the novel coronavirus (SARS-CoV-2) has resulted in a devastating pandemic with global concern. However, to date, there are no regimens to prevent and treat SARS-CoV-2 virus. There is an urgent need to identify novel leads with anti-viral properties that impede viral pathogenesis in the host system. Esculentoside A (EsA), a saponin isolated from the root of Phytolacca esculenta, is known to exhibit diverse pharmacological properties, especially anti-inflammatory activity. To our knowledge, SARS-CoV-2 uses angiotensin converting enzyme 2 (ACE2) to enter host cells. This is mediated through the proteins of SARS-CoV-2, especially the spike glycoprotein receptor binding domain. Thus, our primary goal is to prevent virus replication and binding to the host, which allows us to explore the efficiency of EsA on key surface drug target proteins using the computational biology paradigm approach. Here, the anti-coronavirus activity of EsA in vitro and its potential mode of inhibitory action on the S-protein of SARS-CoV-2 were investigated. We found that EsA inhibited the HCoV-OC43 coronavirus during the attachment and penetration stage. Molecular docking results showed that EsA had a strong binding affinity with the spike glycoprotein from SARS-CoV-2. The results of the molecular dynamics simulation revealed that EsA had higher stable binding with the spike protein. These results demonstrated that Esculentoside A can act as a spike protein blocker to inhibit SARS-CoV-2. Considering the poor bioavailability and low toxicity of EsA, it is suitable as novel lead for the inhibitor against binding interactions of SARS-CoV-2 of S-protein and ACE2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijbiomac.2021.06.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183004PMC
June 2021

Chitotriosidase attenuates brain inflammation via HDAC3/NF-κB pathway in D-galactose and aluminum-induced rat model with cognitive impairments.

Neurosci Res 2021 Jun 7. Epub 2021 Jun 7.

Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China. Electronic address:

Chitotriosidase (CHIT1, chitinase 1) is increased in the cerebrospinal fluid and peripheral blood of Alzheimer's disease (AD) patients. Our previous study has shown that CHIT1 provides potential protection through microglial polarization and reduction of β-amyloid (Aβ) oligomers on rat models of AD. Histone deacetylase 3 (HDAC3) plays a significant role in the expression and regulation of proteins related to the pathophysiology of AD. In addition, nuclear factor-kappa B (NF-κB) signaling pathway activation in neurons is associated with the progression of AD. NF-κB activation is regulated by HDAC3 deacetylation. In the present study, we researched the role of CHIT1 in HDAC3/NF-κB signaling in D-galactose (D-gal) and aluminum-exposed rat model with cognitive impairments. Following CHIT1 treatment, we found that the protein and mRNA levels of HDAC3 and NF-κB were reduced, the expression level of IκBα increased, anti-inflammatory factors (Arg-1, IL-10, and CD206) were elevated while pro-inflammatory factors (TNF-a, iNOS, and IL-1β) were decreased in D-gal/aluminum-induced AD rats. These results indicate that CHIT1 can regulate brain inflammation via HDAC3/NF-κB p65 pathway, contributing to improvement of cognitive impairment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neures.2021.05.014DOI Listing
June 2021

CT-Based Radiomics Signature With Machine Learning Predicts MYCN Amplification in Pediatric Abdominal Neuroblastoma.

Front Oncol 2021 24;11:687884. Epub 2021 May 24.

Department of Radiology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China.

Purpose: MYCN amplification plays a critical role in defining high-risk subgroup of patients with neuroblastoma. We aimed to develop and validate the CT-based machine learning models for predicting MYCN amplification in pediatric abdominal neuroblastoma.

Methods: A total of 172 patients with MYCN amplified (n = 47) and non-amplified (n = 125) were enrolled. The cohort was randomly stratified sampling into training and testing groups. Clinicopathological parameters and radiographic features were selected to construct the clinical predictive model. The regions of interest (ROIs) were segmented on three-phrase CT images to extract first-, second- and higher-order radiomics features. The ICCs, mRMR and LASSO methods were used for dimensionality reduction. The selected features from the training group were used to establish radiomics models using Logistic regression, Support Vector Machine (SVM), Bayes and Random Forest methods. The performance of four different radiomics models was evaluated according to the area under the receiver operator characteristic (ROC) curve (AUC), and then compared by Delong test. The nomogram incorporated of clinicopathological parameters, radiographic features and radiomics signature was developed through multivariate logistic regression. Finally, the predictive performance of the clinical model, radiomics models, and nomogram was evaluated in both training and testing groups.

Results: In total, 1,218 radiomics features were extracted from the ROIs on three-phrase CT images, and then 14 optimal features, including one original first-order feature and eight wavelet-transformed features and five LoG-transformed features, were identified and selected to construct the radiomics models. In the training group, the AUC of the Logistic, SVM, Bayes and Random Forest model was 0.940, 0.940, 0.780 and 0.927, respectively, and the corresponding AUC in the testing group was 0.909, 0.909, 0.729, 0.851, respectively. There was no significant difference among the Logistic, SVM and Random Forest model, but all better than the Bayes model (p <0.005). The predictive performance of the Logistic radiomics model based on three-phrase is similar to nomogram, but both better than the clinical model and radiomics model based on single venous phase.

Conclusion: The CT-based radiomics signature is able to predict MYCN amplification of pediatric abdominal NB with high accuracy based on SVM, Logistic and Random Forest classifiers, while Bayes classifier yields lower predictive performance. When combined with clinical and radiographic qualitative features, the clinics-radiomics nomogram can improve the performance of predicting MYCN amplification.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.687884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181422PMC
May 2021

Unraveling synonymous and deep intronic variants causing aberrant splicing in two genetically undiagnosed epilepsy families.

BMC Med Genomics 2021 Jun 9;14(1):152. Epub 2021 Jun 9.

Cipher Gene, Ltd., Beijing, 100080, China.

Background: Variants identified through parent-child trio-WES yield up to 28-55% positive diagnostic rate across a variety of Mendelian disorders, there remain numerous patients who do not receive a genetic diagnosis. Studies showed that some aberrant splicing variants, which are either not readily detectable by WES or could be miss-interpreted by regular detecting pipelines, are highly relevant to human diseases.

Methods: We retrospectively investigated the negative molecular diagnostics through trio-WES for 15 genetically undiagnosed patients whose clinical manifestations were highly suspected to be genetic disorders with well-established genotype-phenotype relationships. We scrutinized the synonymous variants from WES data and Sanger sequenced the suspected intronic region for deep intronic variants. The functional consequences of variants were analyzed by in vitro minigene experiments.

Results: Here, we report two abnormal splicing events, one of which caused exon truncating due to the activation of cryptic splicing site by a synonymous variant; the other caused partial intron retention due to the generation of splicing sites by a deep intronic variant.

Conclusions: We suggest that, despite initial negative genetic test results in clinically highly suspected genetic diseases, the combination of predictive bioinformatics and functional analysis should be considered to unveil the genetic etiology of undiagnosed rare diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12920-021-01008-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188693PMC
June 2021

Optical Flow Ratio for Assessing Stenting Result and Physiological Significance of Residual Disease.

EuroIntervention 2021 Jun 8. Epub 2021 Jun 8.

Biomedical Instrument Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.

Background: Optical flow ratio (OFR) is a novel method for fast computation of fractional flow reserve (FFR) from optical coherence tomography (OCT) images.

Aims: We aimed to evaluate the accuracy of OFR in predicting post-percutaneous coronary intervention (PCI) FFR and to evaluate the impact of stent expansion on within-stent OFR pressure drop (In-stent OFR).

Methods: Post-PCI OFR was computed in patients with both OCT and FFR interrogation immediately after PCI. Calculation of post-PCI OFR (called simulated residual OFR) from pre-PCI OCT pullbacks after elimination of the stenotic segment by virtual stenting was performed in a subgroup of patients who had pre-PCI OCT images. Stent underexpansion was quantified by the minimum expansion index (MEI) of the stented segment.

Results: A total of 125 paired comparisons between post-PCI OFR and FFR were obtained in 119 patients, among which simulated residual OFR was obtained in 64 vessels. Mean post-PCI FFR was 0.92 ± 0.05. Post-PCI OFR showed good correlation (r = 0.74, p<0.001) and agreement (mean difference = -0.01 ± 0.03, p = 0.051) with FFR. The accuracy in predicting post-PCI FFR≤0.90 was 84% for post-PCI OFR. Simulated residual OFR significantly correlated with post-PCI FFR (r = 0.42, p<0.001). MEI showed moderate correlation (r=-0.49, p<0.001) with In-stent OFR.

Conclusions: Post-PCI OFR showed good diagnostic concordance with post-PCI FFR. Simulated residual OFR significantly correlated with post-PCI FFR. Stent underexpansion significantly correlated with in-stent pressure drop.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4244/EIJ-D-21-00185DOI Listing
June 2021

Hemorrhage and venous thromboembolism in critically ill patients with COVID-19.

SAGE Open Med 2021 31;9:20503121211020167. Epub 2021 May 31.

Department of Vascular Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Objective: The majority of patients with COVID-19 showed mild symptoms. However, approximately 5% of them were critically ill and require intensive care unit admission for advanced life supports. Patients in the intensive care unit were high risk for venous thromboembolism and hemorrhage due to the immobility and anticoagulants used during advanced life supports. The aim of the study was to report the incidence and treatments of the two complications in such patients.

Method: Patients with COVID-19 (Group 1) and patients with community-acquired pneumonia (Group 2) that required intensive care unit admission were enrolled in this retrospective study. Their demographics, laboratory results, ultrasound findings and complications such as venous thromboembolism and hemorrhage were collected and compared.

Results: Thirty-four patients with COVID-19 and 51 patients with community-acquired pneumonia were included. The mean ages were 66 and 63 years in Groups 1 and 2, respectively. Venous thromboembolism was detected in 6 (18%) patients with COVID-19 and 18 (35%) patients with community-acquired pneumonia (P = 0.09). The major type was distal deep venous thrombosis. Twenty-one bleeding events occurred in 12 (35%) patients with COVID-19 and 5 bleeding events occurred in 5 (10%) patients with community-acquired pneumonia, respectively (P = 0.01). Gastrointestinal system was the most common source of bleeding. With the exception of one death due to intracranial bleeding, blood transfusion with or without surgical/endoscopic treatments was able to manage the bleeding in the remaining patients. Multivariable logistic regression showed increasing odds of hemorrhage with extracorporeal membrane oxygenation (odds ratio: 13.9, 95% confidence interval: 4.0-48.1) and COVID-19 (odds ratio: 4.7, 95% confidence interval: 1.2-17.9).

Conclusion: Venous thromboembolism and hemorrhage were common in both groups. The predominant type of venous thromboembolism was distal deep venous thrombosis, which presented a low risk of progression. COVID-19 and extracorporeal membrane oxygenation were risk factors for hemorrhage. Blood transfusion with or without surgical/endoscopic treatments was able to manage it in most cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/20503121211020167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170290PMC
May 2021

Transglutaminase 2 promotes tumorigenicity of colon cancer cells by inactivation of the tumor suppressor p53.

Oncogene 2021 Jun 8. Epub 2021 Jun 8.

Goethe University Hospital Frankfurt, Department of Medicine, Hematology/Oncology, Frankfurt am Main, Germany.

Despite a high clinical need for the treatment of colorectal carcinoma (CRC) as the second leading cause of cancer-related deaths, targeted therapies are still limited. The multifunctional enzyme Transglutaminase 2 (TGM2), which harbors transamidation and GTPase activity, has been implicated in the development and progression of different types of human cancers. However, the mechanism and role of TGM2 in colorectal cancer are poorly understood. Here, we present TGM2 as a promising drug target.In primary patient material of CRC patients, we detected an increased expression and enzymatic activity of TGM2 in colon cancer tissue in comparison to matched normal colon mucosa cells. The genetic ablation of TGM2 in CRC cell lines using shRNAs or CRISPR/Cas9 inhibited cell expansion and tumorsphere formation. In vivo, tumor initiation and growth were reduced upon genetic knockdown of TGM2 in xenotransplantations. TGM2 ablation led to the induction of Caspase-3-driven apoptosis in CRC cells. Functional rescue experiments with TGM2 variants revealed that the transamidation activity is critical for the pro-survival function of TGM2. Transcriptomic and protein-protein interaction analyses applying various methods including super-resolution and time-lapse microscopy showed that TGM2 directly binds to the tumor suppressor p53, leading to its inactivation and escape of apoptosis induction.We demonstrate here that TGM2 is an essential survival factor in CRC, highlighting the therapeutic potential of TGM2 inhibitors in CRC patients with high TGM2 expression. The inactivation of p53 by TGM2 binding indicates a general anti-apoptotic function, which may be relevant in cancers beyond CRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41388-021-01847-wDOI Listing
June 2021

Identification of nodal micrometastasis in colorectal cancer using deep learning on annotation-free whole-slide images.

Mod Pathol 2021 Jun 8. Epub 2021 Jun 8.

aetherAI Co., Ltd., Taipei, Taiwan.

Detection of nodal micrometastasis (tumor size: 0.2-2.0 mm) is challenging for pathologists due to the small size of metastatic foci. Since lymph nodes with micrometastasis are counted as positive nodes, detecting micrometastasis is crucial for accurate pathologic staging of colorectal cancer. Previously, deep learning algorithms developed with manually annotated images performed well in identifying micrometastasis of breast cancer in sentinel lymph nodes. However, the process of manual annotation is labor intensive and time consuming. Multiple instance learning was later used to identify metastatic breast cancer without manual annotation, but its performance appears worse in detecting micrometastasis. Here, we developed a deep learning model using whole-slide images of regional lymph nodes of colorectal cancer with only a slide-level label (either a positive or negative slide). The training, validation, and testing sets included 1963, 219, and 1000 slides, respectively. A supercomputer TAIWANIA 2 was used to train a deep learning model to identify metastasis. At slide level, our algorithm performed well in identifying both macrometastasis (tumor size > 2.0 mm) and micrometastasis with an area under the receiver operating characteristics curve (AUC) of 0.9993 and 0.9956, respectively. Since most of our slides had more than one lymph node, we then tested the performance of our algorithm on 538 single-lymph node images randomly cropped from the testing set. At single-lymph node level, our algorithm maintained good performance in identifying macrometastasis and micrometastasis with an AUC of 0.9944 and 0.9476, respectively. Visualization using class activation mapping confirmed that our model identified nodal metastasis based on areas of tumor cells. Our results demonstrate for the first time that micrometastasis could be detected by deep learning on whole-slide images without manual annotation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41379-021-00838-2DOI Listing
June 2021

Prospective, Single-Center Comparison of Transcranial Direct Current Stimulation Plus Electroacupuncture and Standard Analgesia in Patients After Total Knee Arthroplasty: Effect on Rehabilitation and Functional Recovery.

Med Sci Monit 2021 Jun 9;27:e930363. Epub 2021 Jun 9.

Department of Rehabilitation Medicine, The Affiliated Huai'an Hospital of Xuzhou Medical University and the Second People's Hospital of Huai'an, Huai'an, Jiangsu, China (mainland).

BACKGROUND The aim of this prospective study was to compare transcranial direct current stimulation (tDCS) plus electroacupuncture with standard analgesia in patients after total knee arthroplasty (TKA) to determine the effects on rehabilitation and functional recovery. MATERIAL AND METHODS Eighty patients with osteoarthritis of the knee who underwent TKA were included in the study. They were divided into experimental (n=40) and control groups (n=40) according to postoperative analgesia method. The control group received multimodal analgesia after TKA and the experimental group received additional tDCS plus electroacupuncture. Postoperative pain, knee function, and quality of life were compared between the 2 groups. RESULTS Compared with the control group, the experimental group had significantly lower visual analog scale scores at 3 and 7 days and 3 and 6 weeks after TKA (P<0.05). At 6 weeks after TKA, knee injury and osteoarthritis outcome and Hospital for Special Surgery scores and maximum knee flexion in the experimental group were significantly better than those in the control group (P<0.05). In the experimental group compared with the control group, the Short Form-36 Health Survey score also was significantly increased (P<0.05). CONCLUSIONS The findings from this study showed that tDCS plus electroacupuncture effectively reduced pain after TKA and improved rehabilitation and functional recovery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12659/MSM.930363DOI Listing
June 2021

Sleep disorders in patients with multiple sclerosis in Spain.

Neurologia 2021 Jun 5. Epub 2021 Jun 5.

Multiple Sclerosis Unit, Neurology Service, Vithas Nisa Hospital, 41950 Seville, Spain. Electronic address:

Objective: This study assesses the presence of sleep disturbances and their relationship with clinical and demographic variables in patients with MS, with a view to establishing correlations between the different variables and the frequency of sleep disturbances.

Methods: The Pittsburgh Sleep Quality Index (PSQI) was used to detect sleep disorders. We contacted patients treated at the MS unit and distributed a questionnaire (PSQI) to 221 patients, receiving 142 usable questionnaires between 8 and 30 September 2019.

Results: The prevalence of patients with sleep disturbances in our study was 74.7% (73.7% in women and 76.8% in men). Therefore, sleep disorders are pervasive in patients with MS, with 3 out of 4 patients experiencing them, a higher rate than that observed in the population without the disease. The frequency of sleep disorders gradually increased in line with age. In the 2 age groups analyzed, 44-54 years and 55-68 years, the proportion of moderate and severe sleep disorders was 42.8% and 53.9%, respectively. Moderate and severe sleep disturbances were observed in 27.5%, 44.7%, and 58.3% of patients with Expanded Disability Status Scale scores of 0-3, 3-6, and >6, respectively.

Conclusion: Our results indicate that sleep disorders are more common in patients with MS than in other populations. Patients with secondary progressive forms of MS more frequently present sleep disturbances, while patients with primary progressive forms report them less frequently. Age and degree of disability were positively correlated with the prevalence and severity of sleep disorders in MS patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nrl.2021.03.012DOI Listing
June 2021

Apoptosis in platelets from adult patients with chronic idiopathic thrombocytopenic purpura.

Blood Coagul Fibrinolysis 2021 Jun 7. Epub 2021 Jun 7.

Department of Clinical Laboratory Medicine Division of Urological Surgery Division of Hematology Division of Respirology Department of Blood Purification Department of Pathology Division of Inventional Ultrasonic Therapeutics, the Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong Province, China.

Adult chronic idiopathic thrombocytopenic purpura (cITP) is a chronic and usually life-long haemorrhagic disorder in which enhanced platelet destruction and weakened platelet production lead to thrombocytopenia. Platelets were isolated from blood samples collected from 40 adult patients with cITP and 40 healthy volunteers. Mitochondrial membrane potential (ΔΨm) and plasma membrane phosphatidylserine externalization were determined by flow cytometry, and activation of caspase-3 and expressions of Bax, Bak and Bcl-xL were analysed by western blotting. Flow cytometry showed increased mitochondrial depolarization and lower ΔΨm in platelets from adult patients with cITP. In addition, plasma membrane phosphatidylserine externalization was observed on platelets from adult patients with cITP, but rarely from healthy volunteers. Western blot analysis of platelet proteins revealed that, in adult cITP patients, caspase-3 was activated, which cleaved gelsolin and to release a 47-kDa fragment. Moreover, the expressions of Bax and Bak were elevated, and Bcl-xL was decreased markedly in platelets from adult patients with cITP. Our findings reveal, based on loss of mitochondrial membrane potential (Δψm), phosphatidylserine exposure, caspase-3 activation, enhanced expression of Bax and Bak, and attenuated expression of Bcl-xL, that platelet death in the pathogenesis of thrombocytopenia in chronic ITP in adults is apoptotic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MBC.0000000000001054DOI Listing
June 2021

Investigation of lncRNA-mRNA co-expression network in ETV6-RUNX1-positive pediatric B-cell acute lymphoblastic leukemia.

PLoS One 2021 8;16(6):e0253012. Epub 2021 Jun 8.

Department of Hematology Laboratory, Yantai Yuhuangding Hospital, Yantai, P.R. China.

ETV6/RUNX1 gene fusion is the most common chromosomal translocation abnormality occurred in pediatric B-cell acute lymphoblastic leukemia (B-ALL). Compared with ETV6-RUNX1-negative patients, ETV6-RUNX1-positive patients possess more improved treatment strategies but higher risk to relapse. In this research, the potential gene interaction networks were constructed intending for elucidating the pathogenesis of B-ALL. We performed the weighted gene co-expression network analysis (WGCNA) to assess the involvement of lncRNA-mRNA pairs in B-ALL patients consisting of 24 ETV6-RUNX1-positive patients and 18 ETV6-RUNX1-negative patients and found a module that was significantly associated with positive/negative trait. Gene Ontology analysis showed that mRNAs in this module were enriched in the positive regulation of MAPK cascade, positive regulation of JNK cascade, and myeloid cell differentiation pathway. To further investigate the relationship between lncRNAs and mRNAs in this significant module, we constructed the lncRNA-mRNA co-expression network. 3 lncRNAs (RP11-170J3.2, RP11-135F9.1 and RP1-151B14.9) were found at the core of the lncRNA-mRNA co-expression network, which had the most co-expression connections with mRNAs. And several related mRNAs (ACTN1, TNFRSF21 and NLRP3) had a significant correlation with the patient survival prediction. Our findings may explicate the pathogenesis of B-ALL, and the disease-associated genes could provide clues to find novel biomarkers for prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253012PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186766PMC
June 2021

Ocular manifestations in Chinese adult patients with NLRP3-associated autoinflammatory disease.

Sci Rep 2021 Jun 7;11(1):11904. Epub 2021 Jun 7.

Department of Ophthalmology, Key Laboratory of Ocular Fundus Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.

NLRP3-associated autoinflammatory disease (NLRP3-AID) is a rare autosomal dominant disorder involving multiple systems. We aim to assess the ocular manifestations of Chinese adult patients with NLRP3-AID. Twelve adult patients (> 18 years old) were diagnosed as NLRP3-AID at the Department of Rheumatology, Peking Union Medical College Hospital. All patients underwent ophthalmologic evaluation by an ophthalmologist. Clinical and genetic features of these patients were collected and compared with those from Caucasian population. A total of 7 NLRP3-AID patients (58%) 14 eyes had ocular manifestations. Five NLRP3 variants were identified, and 3 patients (43%) with severe ocular damages were all found to have the NLRP3 T348M variant. The incidences of papilledema and optic atrophy in the Chinese adult NLRP3-AID patients of moderate type were similar to those in the Caucasian NLRP3-AID patients of severe type. This is the first cohort of Chinese adult NLRP3-AID patients with ocular involvement. Ocular manifestations were diverse and even severe in NLRP3-AID, particularly in patients with the moderate phenotype, and may have relationship with genotypes. Awareness of these manifestations by rheumatologists and ophthalmologists could help to avoid the irreversible ocular damages.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-91315-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184759PMC
June 2021

STING inhibitors target the cyclic dinucleotide binding pocket.

Proc Natl Acad Sci U S A 2021 Jun;118(24)

State Key Laboratory of Natural Medicines, Department of Life Science and Technology, China Pharmaceutical University, 211198 Nanjing, China;

Cytosolic DNA activates cGAS (cytosolic DNA sensor cyclic AMP-GMP synthase)-STING (stimulator of interferon genes) signaling, which triggers interferon and inflammatory responses that help defend against microbial infection and cancer. However, aberrant cytosolic self-DNA in Aicardi-Goutière's syndrome and constituently active gain-of-function mutations in STING in STING-associated vasculopathy with onset in infancy (SAVI) patients lead to excessive type I interferons and proinflammatory cytokines, which cause difficult-to-treat and sometimes fatal autoimmune disease. Here, in silico docking identified a potent STING antagonist SN-011 that binds with higher affinity to the cyclic dinucleotide (CDN)-binding pocket of STING than endogenous 2'3'-cGAMP. SN-011 locks STING in an open inactive conformation, which inhibits interferon and inflammatory cytokine induction activated by 2'3'-cGAMP, herpes simplex virus type 1 infection, deficiency, overexpression of cGAS-STING, or SAVI STING mutants. In mice, SN-011 was well tolerated, strongly inhibited hallmarks of inflammation and autoimmunity disease, and prevented death. Thus, a specific STING inhibitor that binds to the STING CDN-binding pocket is a promising lead compound for STING-driven disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.2105465118DOI Listing
June 2021

Effect of first-month head-size growth trajectory on cognitive outcomes in preterm infants.

J Formos Med Assoc 2021 Jun 4. Epub 2021 Jun 4.

Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Pediatrics, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address:

Background: To examine whether the patterns of head-size growth trajectory in the first month after birth are associated with different susceptibility to cognitive impairment outcomes at age 24 months.

Methods: This retrospective cohort study included 590 infants of very-preterm survivors born between 2001 and 2016 receiving neurodevelopmental assessment at age 24 months. 403 children were enrolled for analysis after excluding infants with small-for-gestational age and severe brain injury. The head circumference (HC) growth evaluated weekly in the first month after birth compared to the at-birth HC was analyzed using group-based trajectory modeling. Neurocognition outcomes were determined as normal, borderline delay, or impaired using the Bayley Scales of Infant Development.

Results: The HC growth dynamics in the first month after birth showed three trajectory patterns: delayed catch-up (31.5%), slow catch-up (54.0%), and fast catch-up (14.5%), which significantly corresponded to different rates of impaired cognition at 19.5%, 6.0%, and 8.5%, respectively (p < 0.001). While 60% of the fast catch-up group had normal cognition, only one-third of the delayed catch-up group showed normal cognition. Three neonatal risk factors, gestational age (p = 0.006), respiratory distress syndrome requiring surfactant therapy (p = 0.012), and hemodynamically significant patent ductus arteriosus requiring intervention (p = 0.047) significantly affected HC growth trajectory patterning that led to cognitive impairment outcomes at follow-up.

Conclusions: Preterm infants with delayed catch-up of head-size growth in the first month of age is susceptible to cognitive impairment outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jfma.2021.05.013DOI Listing
June 2021

Estrogen/ER in anti-tumor immunity regulation to tumor cell and tumor microenvironment.

Cancer Cell Int 2021 Jun 7;21(1):295. Epub 2021 Jun 7.

Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, #88 Jiefang Road, Hangzhou, 310009, Zhejiang, People's Republic of China.

As the essential sexual hormone, estrogen and its receptor has been proved to participate in the regulation of autoimmunity diseases and anti-tumor immunity. The adjustment of tumor immunity is related to the interaction between cancer cells, immune cells and tumor microenvironment, all of which is considered as the potential target in estrogen-induced immune system regulation. However, the specific mechanism of estrogen-induced immunity is poorly understood. Typically, estrogen causes the nuclear localization of estrogen/estrogen receptor complex and alternates the transcription pattern of target genes, leading to the reprogramming of tumor cells and differentiation of immune cells. However, the estrogen-induced non-canonical signal pathway activation is also crucial to the rapid function of estrogen, such as NF-κB, MAPK-ERK, and β-catenin pathway activation, which has not been totally illuminated. So, the investigation of estrogen modulatory mechanisms in these two manners is vital for the tumor immunity and can provide the potential for endocrine hormone targeted cancer immunotherapy. Here, this review summarized the estrogen-induced canonical and non-canonical signal transduction pathway and aimed to focus on the relationship among estrogen and cancer immunity as well as immune-related tumor microenvironment regulation. Results from these preclinical researches elucidated that the estrogen-target therapy has the application prospect of cancer immunotherapy, which requires the further translational research of these treatment strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12935-021-02003-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182917PMC
June 2021