Publications by authors named "Qi Tang"

374 Publications

Sequence Dependent Repair of 1,-Ethenoadenine by DNA Repair Enzymes ALKBH2, ALKBH3, and AlkB.

Molecules 2021 Aug 31;26(17). Epub 2021 Aug 31.

Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA.

Mutation patterns of DNA adducts, such as mutational spectra and signatures, are useful tools for diagnostic and prognostic purposes. Mutational spectra of carcinogens derive from three sources: adduct formation, replication bypass, and repair. Here, we consider the repair aspect of 1,-ethenoadenine (εA) by the 2-oxoglutarate/Fe(II)-dependent AlkB family enzymes. Specifically, we investigated εA repair across 16 possible sequence contexts (5'/3' flanking base to εA varied as G/A/T/C). The results revealed that repair efficiency is altered according to sequence, enzyme, and strand context (ss- versus ds-DNA). The methods can be used to study other aspects of mutational spectra or other pathways of repair.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules26175285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434105PMC
August 2021

Efficient access to aliphatic esters by photocatalyzed alkoxycarbonylation of alkenes with alkyloxalyl chlorides.

Nat Commun 2021 Sep 7;12(1):5328. Epub 2021 Sep 7.

School of Pharmaceutical and Materials Engineering & Institute for Advanced Studies, Taizhou University, Taizhou, China.

Aliphatic esters are essential constituents of biologically active compounds and versatile chemical intermediates for the synthesis of drugs. However, their preparation from readily available olefins remains challenging. Here, we report a strategy to access aliphatic esters from olefins through a photocatalyzed alkoxycarbonylation reaction. Alkyloxalyl chlorides, generated in situ from the corresponding alcohols and oxalyl chloride, are engaged as alkoxycarbonyl radical fragments under photoredox catalysis. This transformation tolerates a broad scope of electron-rich and electron-deficient olefins and provides the corresponding β-chloro esters in good yields. Additionally, a formal β-selective alkene alkoxycarbonylation is developed. Moreover, a variety of oxindole-3-acetates and furoindolines are prepared in good to excellent yields. A more concise formal synthesis of (±)-physovenine is accomplished as well. With these strategies, a wide range of natural-product-derived olefins and alkyloxalyl chlorides are also successfully employed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-25628-xDOI Listing
September 2021

Physiological Functions of Threonine in Animals: Beyond Nutrition Metabolism.

Nutrients 2021 Jul 28;13(8). Epub 2021 Jul 28.

State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.

Threonine (Thr), an essential amino acid for animals and the limiting amino acid in swine and poultry diets, which plays a vital role in the modulation of nutritional metabolism, macromolecular biosynthesis, and gut homeostasis. Current evidence supports that the supplementation of Thr leads to benefits in terms of energy metabolism. Threonine is not only an important component of gastrointestinal mucin, but also acts as a nutritional modulator that influences the intestinal immune system via complex signaling networks, particularly mitogen-activated protein kinase (MAPK) and the target of the rapamycin (TOR) signal pathway. Threonine is also recognized as an indispensable nutrient for cell growth and proliferation. Hence, optimization of Thr requirement may exert a favorable impact on the factors linked to health and diseases in animals. This review focuses on the latest reports of Thr in metabolic pathways and nutritional regulation, as well as the relationship between Thr and relevant physiological functions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu13082592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399342PMC
July 2021

Targeted deletion of Atoh8 results in severe hearing loss in mice.

Genesis 2021 Sep 17;59(9):e23442. Epub 2021 Aug 17.

Department of Otolaryngology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Atoh8, also named Math6, is a bHLH gene reported to have important functions in the developing nervous system, pancreas and kidney. However, the expression pattern and function of Atoh8 in the inner ear are still unclear. To study the function of Atoh8 in the developing mouse inner ear, we performed targeted deletion of Atoh8 by intercrossing Atoh8 mice. We studied the expression pattern of Atoh8 in the inner ear and found interesting results that Atoh8-null (Atoh8 ) mice were viable but smaller than their littermates and they were severely hearing impaired, which was confirmed by hearing tests (ABR, DPOAE). We collected 129 viable newborns from 18 litters by crossing Atoh8 mice and found that the distributions of Atoh8 , Atoh8 and wild type were very close to their expected Mendelian ratio by χ testing. However, no remarkable morphological changes in cochleae in mutant mice were detected under plastic sectioning and electron microscopy. No remarkable differences in the expression of Myosin6, Prestin, TrkC, GAD65, Tuj1, or Calretinin were detected between the mutant mice and the control mice. These findings indicate that Atoh8 plays an important role in the development of normal hearing, while further studies are required to elucidate its exact function in hearing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/dvg.23442DOI Listing
September 2021

Changes of trabecular meshwork pigmentation in patients with pigment dispersion syndrome: A 15-year study.

Medicine (Baltimore) 2021 Aug;100(31):e26567

Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Lab.

Abstract: To report the changes of trabecular meshwork (TM) pigmentation and clinical outcomes of patients with pigment dispersion syndrome (PDS) after resolution of reverse pupillary block.Twenty one eyes of 11 PDS patients were followed up periodically for 15 years after resolution of reverse pupillary block with either Nd: YAG laser peripheral iridotomy (LPI) or trabeculectomy. Visual acuity (VA), best-corrected visual acuity (BCVA), slit lamp examination, intraocular pressure (IOP), Humphrey visual field analysis (VFA), gonioscopy and stereoscopic funduscopy were performed on admission and every 6 months postoperatively. TM pigmentation was quantitatively evaluated and graded every 5 years after the treatment, in which the circumference of anterior chamber angle was divided into 4 quadrants: superior, inferior, nasal and temporal. Postoperative IOP, VA, BCVA, VFA, TM pigmentation and adjunctive anti-glaucoma medications were main outcome measurements and compared with baseline.Eleven patients (9 males, 2 females) were identified as PDS according to the diagnostic criteria, with average age of 38.25 ± 6.93 years (range, 31-55 years) at initial diagnosis. The mean IOP level was 33.1 ± 9.8 mmHg (range, 22-56 mmHg) at diagnosis. Ten PDS eyes received LPI, and the other eleven eyes underwent uneventful trabeculectomy. The median TM pigmentation score of the 21 PDS eyes was 16 (interquartile range [IQR], 15-16) on admission, which changed to 14 (IQR, 13-15), 13 (IQR, 12-14), 12(IQR, 10.5-12) at 5-, 10-, 15-year follow-up visits respectively. The decrease rate of TM pigmentation was 37% in inferior quadrant, while in nasal, temporal, and superior quadrant the reduction rate was 28%, 23%, and 18%, respectively, at the last follow-up visit. Majority of these enrolled eyes (19/21) had stable VA and BCVA with average endpoint IOP of 15.1 ± 3.4 mmHg.TM pigmentation in PDS patients attenuates with time after reverse pupillary block was resolved, in which the inferior quadrant seems faster than the other quadrants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000026567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341214PMC
August 2021

Children of parents with mental illness in the COVID-19pandemic: A cross-sectional survey in China.

Asian J Psychiatr 2021 Oct 4;64:102801. Epub 2021 Aug 4.

Peking University Sixth Hospital, Peking University Institute of Mental Health, T++he Key Laboratory of the Ministry of Health (Peking University), National Clinical Research Center for Mental Disorders, Beijing, China. Electronic address:

Objective: Children of parents with mental illness (COPMI) are vulnerable during the COVID-19 pandemic. The study aimed to assess the psychosocial impacts of the pandemic and identify potential factors influencing their mental health.

Method: 665 COPMI from six sites including Wuhan in China were enrolled. COPMI's mental health and the impacts of COVID-19 were assessed by an online survey. Univariate and multivariate analyses were performed to examine the association between impact factors and participants' mental health.

Results: 16.1 % of participants were in abnormal range of mental health, with interpersonal relationship being the most common problem. 48.6 % of participants reported quite worried about the epidemic. All aspects of adverse effects of COVID-19 were more prevalent among COPMI in Wuhan than in other sites. Concerns about COVID-19 (OR = 1.7, p = 0.02), decreased family income (OR = 2.0, p = 0.02), being physically abused (OR = 2.1, p = 0.04), witnessing family members being physically abused (OR = 2.0, p = 0.03), and needs for promoting family members' mental health (OR = 2.2, p < 0.01) were independent risk factors for participants' mental health.

Conclusion: The findings raise our awareness of the impacts of COVID-19 pandemic on the wellbeing of COPMI. Multifaceted psychosocial support for COPMI is urgently needed to support them live through the pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajp.2021.102801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419216PMC
October 2021

Lamivudine improves cognitive decline in SAMP8 mice: Integrating in vivo pharmacological evaluation and network pharmacology.

J Cell Mol Med 2021 Sep 10;25(17):8490-8503. Epub 2021 Aug 10.

Department of Clinical Laboratory, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

The reverse transcriptase inhibitors such as lamivudine (3TC) play important roles in anti-ageing, but their effects on neurodegenerative diseases caused by ageing are not clear, especially on the functions of the nervous system such as cognition. In this study, we administered 3TC to senescence-accelerated mouse prone 8 (SAMP8) mice by gastric perfusion (100 mg/kg) for 4 weeks. Our results showed that 3TC significantly improved the ageing status of SAMP8 mice, especially the decline of cognitive ability evaluated by the Morris water maze test. To further investigate the molecular mechanisms of improving the ageing status of SAMP8 mice by 3TC, the qPCR and tissue staining methods were used to study the brain tissues (i.e., hippocampus and cortex) of mice, while the network pharmacology analysis was applied to investigate the potential targets of 3TC. The results showed that the mRNA levels of genes related to long interspersed element-1, type 1 interferon response, the senescence-associated secretion phenotype and the Alzheimer's disease in the hippocampus and cortex of SAMP8 mice were increased due to senescence, but this trend was reversed partially by 3TC. Results of histological studies showed that 3TC reduced the death of hippocampal neurons, while the results of network pharmacology analysis indicated that 3TC may exert its influence through multiple pathways, including the oestrogen signalling and the PI3K/Akt and neuroactive ligand-receptor interaction signalling pathways, which we have verified through in vitro experiments. These findings provide evidence for the therapeutic potential of 3TC in the treatment of neurodegenerative diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jcmm.16811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419189PMC
September 2021

Maize DNA Methylation in Response to Drought Stress Is Involved in Target Gene Expression and Alternative Splicing.

Int J Mol Sci 2021 Jul 31;22(15). Epub 2021 Jul 31.

State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University, Chengdu 611130, China.

DNA methylation is important for plant growth, development, and stress response. To understand DNA methylation dynamics in maize roots under water stress (WS), we reanalyzed DNA methylation sequencing data to profile DNA methylation and the gene expression landscape of two inbred lines with different drought sensitivities, as well as two of their derived recombination inbred lines (RILs). Combined with genotyping-by-sequencing, we found that the inheritance pattern of DNA methylation between RILs and parental lines was sequence-dependent. Increased DNA methylation levels were observed under WS and the methylome of drought-tolerant inbred lines were much more stable than that of the drought-sensitive inbred lines. Distinctive differentially methylated genes were found among diverse genetic backgrounds, suggesting that inbred lines with different drought sensitivities may have responded to stress in varying ways. Gene body DNA methylation showed a negative correlation with gene expression but a positive correlation with exon splicing events. Furthermore, a positive correlation of a varying extent was observed between small interfering RNA (siRNA) and DNA methylation, which at different genic regions. The response of siRNAs under WS was consistent with the differential DNA methylation. Taken together, our data can be useful in deciphering the roles of DNA methylation in plant drought-tolerance variations and in emphasizing its function in alternative splicing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22158285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8347047PMC
July 2021

GATA3 maintains the quiescent state of cochlear supporting cells by regulating p27.

Sci Rep 2021 Aug 4;11(1):15779. Epub 2021 Aug 4.

Department of Ophthalmology and Flaum Eye Institute, University of Rochester, Rochester, NY, 14642, USA.

Haplo-insufficiency of the GATA3 gene causes hypoparathyroidism, sensorineural hearing loss, and renal disease (HDR) syndrome. Previous studies have shown that Gata3 is required for the development of the prosensory domain and spiral ganglion neurons (SGNs) of the mouse cochlea during embryogenesis. However, its role in supporting cells (SCs) after cell fate specification is largely unknown. In this study, we used tamoxifen-inducible Sox2 mice to delete Gata3 in SCs of the neonatal mouse cochlea and showed that loss of Gata3 resulted in the proliferation of SCs, including the inner pillar cells (IPCs), inner border cells (IBCs), and lateral greater epithelium ridge (GER). In addition, loss of Gata3 resulted in the down-regulation of p27, a cell cycle inhibitor, in the SCs of Gata3-CKO neonatal cochleae. Chromatin immunoprecipitation analysis revealed that GATA3 directly binds to p27 promoter and could maintain the quiescent state of cochlear SCs by regulating p27 expression. Furthermore, RNA-seq analysis revealed that loss of Gata3 function resulted in the change in the expression of genes essential for the development and function of cochlear SCs, including Tectb, Cyp26b1, Slitrk6, Ano1, and Aqp4.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-95427-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8338922PMC
August 2021

Glycan Labeling and Analysis in Cells and In Vivo.

Annu Rev Anal Chem (Palo Alto Calif) 2021 07 27;14(1):363-387. Epub 2021 Jul 27.

College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China; email:

As one of the major types of biomacromolecules in the cell, glycans play essential functional roles in various biological processes. Compared with proteins and nucleic acids, the analysis of glycans in situ has been more challenging. Herein we review recent advances in the development of methods and strategies for labeling, imaging, and profiling of glycans in cells and in vivo. Cellular glycans can be labeled by affinity-based probes, including lectin and antibody conjugates, direct chemical modification, metabolic glycan labeling, and chemoenzymatic labeling. These methods have been applied to label glycans with fluorophores, which enables the visualization and tracking of glycans in cells, tissues, and living organisms. Alternatively, labeling glycans with affinity tags has enabled the enrichment of glycoproteins for glycoproteomic profiling. Built on the glycan labeling methods, strategies enabling cell-selective and tissue-specific glycan labeling and protein-specific glycan imaging have been developed. With these methods and strategies, researchers are now better poised than ever to dissect the biological function of glycans in physiological or pathological contexts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-anchem-091620-091314DOI Listing
July 2021

Palliative effects of metformin on testicular damage induced by triptolide in male rats.

Ecotoxicol Environ Saf 2021 Oct 22;222:112536. Epub 2021 Jul 22.

College of Animal Science and Technology, Northwest A&F University, Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, Key Laboratory of Animal Biotechnology, Ministry of Agriculture, No. 22 Xinong Road, Yangling, Shaanxi 712100, PR China. Electronic address:

As a widely existing traditional Chinese medicine component, TP (triptolide) has serious reproductive toxicity which causes severe damage to the reproductive system and limits its application prospect. TP and MET (metformin) have shown great potential in combined with each other in anticancer and anti-inflammatory. Whether metformin can resist the reproductive toxicity caused by triptolide, the effects of MET on TP-induced reproductive capacity has not been reported. In this study, metformin was used to investigate the therapeutic effect on reproductive toxicity induced by TP in rat. The results showed that metformin had significant therapeutic effects on oxidative stress damage, destruction of the blood-testosterone barrier and apoptosis. And it proved that its therapeutic effect is mainly to restore the structural and functional stability of testis through antioxidant stress. It will provide guidance for the treatment of reproductive toxicity caused by TP and the adjuvant detoxification of TP application.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ecoenv.2021.112536DOI Listing
October 2021

ANXA2 Facilitates Enterovirus 71 Infection by Interacting with 3D Polymerase and PI4KB to Assist the Assembly of Replication Organelles.

Virol Sin 2021 Jul 1. Epub 2021 Jul 1.

State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, 430072, China.

Similar to that of other enteroviruses, the replication of enterovirus 71 (EV71) occurs on rearranged membranous structures called replication organelles (ROs). Phosphatidylinositol 4-kinase III (PI4KB), which is required by enteroviruses for RO formation, yields phosphatidylinositol-4-phosphate (PI4P) on ROs. PI4P then binds and induces conformational changes in the RNA-dependent RNA polymerase (RdRp) to modulate RdRp activity. Here, we targeted 3D polymerase, the core enzyme of EV71 ROs, and found that the host factor Annexin A2 (ANXA2) can interact with 3D polymerase and promote the replication of EV71. Then, an experiment showed that the annexin domain of ANXA2, which possesses membrane-binding capacity, mediates the interaction of ANXA2 with EV71 3D polymerase. Further research showed that ANXA2 is localized on ROs and interacts with PI4KB. Overexpression of ANXA2 stimulated the formation of PI4P, and the level of PI4P was decreased in ANXA2-knockout cells. Furthermore, ANXA2, PI4KB, and 3D were shown to be localized to the viral RNA replication site, where they form a higher-order protein complex, and the presence of ANXA2 promoted the PI4KB-3D interaction. Altogether, our data provide new insight into the role of ANXA2 in facilitating formation of the EV71 RNA replication complex.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12250-021-00417-4DOI Listing
July 2021

China should emphasize key issues inherent in rational medication management for the elderly.

Biosci Trends 2021 Jul 1. Epub 2021 Jul 1.

School of Public Health, Fudan University, Shanghai, China.

According to China's Seventh National Census, 18.70% of a total of 1.41 billion people were 60 or older and 13.50% were 65 or older, so China's population is increasingly aging. In conjunction with China's socioeconomic and scientific and technological development and its promotion of medical insurance-related policies, rational medication management for the elderly is a concern in order to control the risk of polypharmacy. This paper summarizes and discusses the following five key issues inherent in rational medication management: i) an increase in serious polypharmacy and the potential risks of medication; ii) a lack of medication consultation service and medication withdraw without healthcare providers' supervision; iii) poor medication compliance among the elderly; iv) insufficient quantity and incompetence of pharmaceutical staffing; and v) limited awareness of pharmaceutical services and lack of trust in the ability of pharmacists. Based on a discussion of factors influencing these issues, suggestions have been put forward in the hopes that China emphasizes rational medication management in order to reduce the risk of polypharmacy and the disease burden of the elderly in China.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5582/bst.2021.01254DOI Listing
July 2021

Characterization of a bacterial strain Lactobacillus paracasei LP10266 recovered from an endocarditis patient in Shandong, China.

BMC Microbiol 2021 06 17;21(1):183. Epub 2021 Jun 17.

Department of Clinical Laboratory, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China.

Background: Lactobacilli are often recognized as beneficial partners in human microbial environments. However, lactobacilli also cause diseases in human, e.g. infective endocarditis (IE), septicaemia, rheumatic vascular disease, and dental caries. Therefore, the identification of potential pathogenic traits associated with lactobacilli will facilitate the prevention and treatment of the diseases caused by lactobacilli. Herein, we investigated the genomic traits and pathogenic potential of a novel bacterial strain Lactobacillus paracasei LP10266 which has caused a case of IE. We isolated L. paracasei LP10266 from an IE patient's blood to perform high-throughput sequencing and compared the genome of strain LP10266 with those of closely related lactobacilli to determine genes associated with its infectivity. We performed the antimicrobial susceptibility testing on strain LP10266. We assessed its virulence by mouse lethality and serum bactericidal assays as well as its serum complement- and platelet-activating ability. The biofilm formation and adherence of strain LP10266 were also studied.

Results: Phylogenetic analysis revealed that strain LP10266 was allied with L. casei and L. paracasei. Genomic studies revealed two spaCBA pilus clusters and one novel exopolysaccharides (EPS) cluster in strain LP10266, which was sensitive to ampicillin, penicillin, levofloxacin, and imipenem, but resistant to cefuroxime, cefazolin, cefotaxime, meropenem, and vancomycin. Strain LP10266 was nonfatal and sensitive to serum, capable of activating complement 3a and terminal complement complex C5b-9 (TCC). Strain LP10266 could not induce platelet aggregation but displayed a stronger biofilm formation ability and adherence to human vascular endothelial cells (HUVECs) compared to the standard control strain L. paracasei ATCC25302.

Conclusion: The genome of a novel bacterial strain L. paracasei LP10266 was sequenced. Our results based on various types of assays consistently revealed that L. paracasei LP10266 was a potential pathogen to patients with a history of cardiac disease and inguinal hernia repair. Strain LP10266 showed strong biofilm formation ability and adherence, enhancing the awareness of L. paracasei infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12866-021-02253-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210379PMC
June 2021

The miR-302c/transforming growth factor-β receptor type-2 axis modulates interleukin-1β-induced degenerative changes in osteoarthritic chondrocytes.

J Cell Commun Signal 2021 Jun 14. Epub 2021 Jun 14.

Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China.

Chondrocyte production of catabolic and inflammatory mediators participating in extracellular matrix degradation has been regarded as a central event in osteoarthritis (OA) development. During OA pathogenesis, interleukin-1β (IL-1β) decreases the mRNA expression and protein levels of transforming growth factor-β receptor type-2 (TGFBR2), thus disrupting transforming growth factor-β signaling and promoting OA development. In the present study, we attempted to identify the differentially expressed genes in OA chondrocytes upon IL-1β treatment, investigate their specific roles in OA development, and reveal the underlying mechanism. As shown by online data analysis and experimental results, TGFBR2 expression was significantly downregulated in IL-1β-treated human primary OA chondrocytes. IL-1β treatment induced degenerative changes in OA chondrocytes, as manifested by increased matrix metalloproteinase 13 and a disintegrin and metalloproteinase with thrombospondin motifs 5 proteins, decreased Aggrecan and Collagen II proteins, and suppressed OA chondrocyte proliferation. These degenerative changes were significantly reversed by TGFBR2 overexpression. miR-302c expression was markedly induced by IL-1β treatment in OA chondrocytes. miR-302c suppressed the expression of TGFBR2 via direct binding to its 3'- untranslated region. Similar to TGFBR2 overexpression, miR-302c inhibition significantly improved IL-1β-induced degenerative changes in OA chondrocytes. Conversely, TGFBR2 silencing enhanced IL-1β-induced degenerative changes and significantly reversed the effects of miR-302c inhibition in response to IL-1β treatment. In conclusion, the miR-302c/TGFBR2 axis could modulate IL-1β-induced degenerative changes in OA chondrocytes and might become a novel target for OA treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12079-020-00591-2DOI Listing
June 2021

A 7-nt nucleotide sequence variant within the sheep gene affects female reproduction traits.

Anim Biotechnol 2021 Jun 3:1-7. Epub 2021 Jun 3.

Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.

Lysine demethylase 3B () gene is a histone demethylase, demonstrating specific demethylation of the histone H3 lysine 9. It was detected as a sheep reproductive candidate gene by genome-wide scans, and related studies also showed its significance in female reproductive process. However, rare study researched its polymorphism. Herein, we hypothesized that the polymorphisms of gene were associated with sheep reproduction traits. A 7-nt nucleotide sequence variant (rs1088697156) within gene was identified in a total of 888 individuals, including the Australian White (AUW) sheep and Lanzhou Fat-tailed (LFT) sheep. II (insertion/insertion) and ID (insertion/deletion) genotypes of 7-nt variant were detected, which were at Hardy-Weinberg equilibrium (HWE) in detected breeds. Association analysis illustrated the 7-nt variant was significantly associated with the litter size, duration of pregnancy, live lamb number, live lamb rate, stillbirth number, stillbirth rate of average and different parity ( < 0.05) in AUW sheep. Moreover, 'ID' was the dominant genotype with excellent consistency in reproductive traits. It is instrumental to select individuals with ID genotype for improving the sheep reproduction traits. These findings suggest that the 7-nt variant within gene can be used as a candidate marker of reproduction traits for sheep breeding improvement by marker-assisted selection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10495398.2021.1929270DOI Listing
June 2021

The protein corona and its effects on nanoparticle-based drug delivery systems.

Acta Biomater 2021 07 25;129:57-72. Epub 2021 May 25.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China. Electronic address:

In most cases, once nanoparticles (NPs) enter the blood, their surface is covered by biological molecules, especially proteins, forming a so-called protein corona (PC). As a result, what the cells of the body "see" is not the NPs as formulated by the chemists, but the PC. In this way, the PC can influence the effects of the NPs and even mask the desired effects of the NP components. While this can argue for trying to inhibit protein-nanomaterial interactions, encapsulating NPs in an endogenous PC may increase their clinical usefulness. In this review, we briefly introduce the concept of the PC, its formation and its effects on the behavior of NPs. We also discuss how to reduce the formation of PCs or exploit them to enhance NP functions. Studying the interactions between proteins and NPs will provide insights into their clinical activity in health and disease. STATEMENT OF SIGNIFICANCE: The formation of protein corona (PC) will affect the operation of nanoparticles (NPs) in vivo. Since there are many proteins in the blood, it is impossible to completely overcome the formation of PC. Therefore, the use of PCs to deliver drug is the best choice. De-opsonins adsorbed on NPs can reduce macrophage phagocytosis and cytotoxicity of NPs, and prolong their circulation in blood. Albumin, apolipoprotein and transferrin are typical de-opsonins. In present review, we mainly discuss how to optimize the delivery of nanoparticles through the formation of albumin corona, transferrin corona and apolipoprotein corona in vivo or in vitro.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.actbio.2021.05.019DOI Listing
July 2021

The effect of microbial composition and proteomic on improvement of functional constipation by Chrysanthemum morifolium polysaccharide.

Food Chem Toxicol 2021 Jul 23;153:112305. Epub 2021 May 23.

National R & D Center for Edible Fungus Processing Technology, Henan University, Kaifeng, 475004, China; Functional Food Engineering Technology Research Center, Kaifeng, 475004, China. Electronic address:

In this paper, SD rat constipation model was established with loperamide hydrochloride to study the effect of Chrysanthemum morifolium polysaccharide on the improvement of functional constipation, and the mechanism of improving constipation was investigated with the proteomics and intestinal flora. The results showed that the HD group of C. morifolium polysaccharide could significantly increase the levels of water content of stool pellets, small intestine propulsion rate, gastrin (MTL), gastrin (GAS) and substance P (SP), decrease the level of growth inhibitor (SS) and improved gastrointestinal motility in rats. Gut microbial studies showed that C. morifolium polysaccharide could significantly increase species abundance and flora diversity and improve flora structure. The relative abundance of Lactobacillus and Romboutsia increased, while the relative abundance of Lachnospiraceae_NK4A136_group and Roseburia decreased compared with the MC group. Proteomics studies suggested that C. morifolium polysaccharides could reduce intestinal lesions, enhance intestinal homeostasis, increase amino acid uptake, promote intestinal motility and relieve constipation by regulating the expression of RAS, FABP1 and SLC1A5 proteins.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fct.2021.112305DOI Listing
July 2021

Brassinosteroids inhibit miRNA-mediated translational repression by decreasing AGO1 on the endoplasmic reticulum.

J Integr Plant Biol 2021 Aug 22;63(8):1475-1490. Epub 2021 Jun 22.

State Key Laboratory of Genetic Engineering, Ministry of Education Key Laboratory of Biodiversity Sciences and Ecological Engineering, Collaborative Innovation Center of Genetics and Development, Institute of Plant Biology, School of Life Sciences, Fudan University, Shanghai, 200438, China.

Translational repression is a conserved mechanism in microRNA (miRNA)-guided gene silencing. In Arabidopsis, ARGONAUTE1 (AGO1), the major miRNA effector, localizes in the cytoplasm for mRNA cleavage and at the endoplasmic reticulum (ER) for translational repression of target genes. However, the mechanism underlying miRNA-mediated translational repression is poorly understood. In particular, how the subcellular partitioning of AGO1 is regulated is largely unexplored. Here, we show that the plant hormone brassinosteroids (BRs) inhibit miRNA-mediated translational repression by negatively regulating the distribution of AGO1 at the ER in Arabidopsis thaliana. We show that the protein levels rather than the transcript levels of miRNA target genes were reduced in BR-deficient mutants but increased under BR treatments. The localization of AGO1 at the ER was significantly decreased under BR treatments while it was increased in the BR-deficient mutants. Moreover, ROTUNDIFOLIA3 (ROT3), an enzyme involved in BR biosynthesis, co-localizes with AGO1 at the ER and interacts with AGO1 in a GW motif-dependent manner. Complementation analysis showed that the AGO1-ROT3 interaction is necessary for the function of ROT3. Our findings provide new clues to understand how miRNA-mediated gene silencing is regulated by plant endogenous hormones.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jipb.13139DOI Listing
August 2021

Mitochondria-targeted carbon monoxide delivery combined with singlet oxygen production from a single nanoplatform under 808 nm light irradiation for synergistic anticancer therapy.

J Mater Chem B 2021 05;9(20):4241-4248

Key Laboratory for Advanced Materials, School of Chemistry & Molecular Engineering, East China University of Science and Technology, Shanghai 200237, P. R. China.

A multifunctional nanoplatform (1), [email protected]@C-TiO2, which consists of a carrier of carbon-doped TiO2 nanoparticles with surface covalent functionalization of manganese carbonyls and a directing group of triphenylphosphine, was prepared for mitochondria-targeted carbon monoxide (CO) delivery combined with photodynamic therapy (PDT). [email protected]@C-TiO2 selectively localized in the mitochondria of HeLa cells where the overexpressed-H2O2 triggered CO release resulting in mitochondrial damage. And singlet oxygen species generated upon 808 nm near infrared light irradiation further destroyed the mitochondria and induced cancer cells apoptosis. Cytotoxicity assays revealed that the nanoplatform with mitochondria-targeted CO delivery and PDT exhibited the highest lethality against cancer cells in comparison with all the other control samples tested, and it showed good dark biocompatibility with normal cells that express low H2O2 levels. This work may provide new insights into combining CO-based gas therapy with traditional PDT for efficient cancer treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1tb00478fDOI Listing
May 2021

Hub Genes Associated with the Diagnosis of Diabetic Retinopathy.

Int J Gen Med 2021 6;14:1739-1750. Epub 2021 May 6.

Department of Ophthalmology, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530022, People's Republic of China.

Purpose: This study aimed to identify genes that may be effective in diagnosing or treating diabetic retinopathy (DR), the most common complication of diabetes mellitus (DM).

Methods: Differentially expressed genes (DEGs) were identified between DR and DM in GSE146615 dataset. DEGs that were consistently up- or down-regulated under both standard glucose and high glucose conditions were identified as common genes and used to generate a protein-protein interaction network and modules. The module genes were assessed for the area under the receiver operating characteristic curve (AUC), leading to the identification of hub genes. Differentially methylated probes in GSE76169 were also compared with common DEGs to identify specific methylation markers of DR. Enrichment analysis was used to explore the biological characteristics. The Short Time-series Expression Miner algorithm was used to identify genes that were progressively dysregulated in the sequence: healthy controls < DM < DR.

Results: A total of 1917 common genes were identified for seven modules. The eight genes with AUC > 0.8 under high glucose and standard glucose conditions were considered as hub genes. The module genes were significantly enriched during vascular smooth muscle cell development and regulation of oxygen metabolism, while 92 methylation markers were involved in the similar terms. Among the progressively dysregulated genes, three intersection genes under both standard glucose and high glucose conditions were found to be module genes and were considered as key genes.

Conclusion: We identified eight potential DR-specific diagnostic and therapeutic genes, whose abnormal expression can cause oxidative stress, thus favoring the course of the disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/IJGM.S311683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110263PMC
May 2021

Smoothened loss is a characteristic of neuroendocrine prostate cancer.

Prostate 2021 Jun 6;81(9):508-520. Epub 2021 May 6.

Department of Clinical Laboratory, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Purpose: Hedgehog (Hh) signaling promotes castration-resistant prostate cancer by supporting androgen-independent prostate cancer cell development and growth; however, its role in neuroendocrine prostate cancer (NEPC) has not yet been explored. In this study, we assessed the expression of key genes involved in Hh signaling in prostate cancer and investigated the potential role of smoothened (SMO) in the pathogenesis of NEPC.

Methods: Six public datasets, each containing cases of prostate adenocarcinoma (AdPC) and NEPC, were analyzed to compare the differential messenger RNA (mRNA) expression of six classic Hh signaling genes. The SMO, synaptophysin, chromogranin A (CHGA) and androgen receptor (AR) proteins were evaluated in human tissues from 5 cases of NEPC, 2 cases of AdPC mixed with NEPC, 2 cases of AdPC with neuroendocrine differentiation and 22 cases of high-grade AdPC as determined by an immunohistochemistry assay. Gene set enrichment analysis (GSEA) was performed to identify relevant genetic signatures associated with SMO expression based on the public datasets. Stable SMO-knockdown LNCaP and C4-2B cells were established with a lentiviral system, and the expression of SMO, Gli1, AR, prostate-specific antigen (PSA), and REST was assessed by real-time polymerase chain reaction and western blot. Secreted PSA in the conditioned medium was assessed by ELISA. Gli1 was ectopically expressed performed by the transfection of Gli1 complementary DNA into SMO-knockdown LNCaP cells, and western blot was used to assess of AR and PSA expression.

Results: The mRNA level of SMO was dramatically downregulated in NEPC samples compared with AdPC samples in all 6 public datasets. SMO protein loss was observed in 100% of NEPC samples but in only 9% (2 of 22) of high-grade AdPC samples. GSEA results showed that SMO loss was closely correlated with AR signaling activity. Stable SMO knockdown significantly attenuated AR signaling activity and suppressed AR expression, while Gli1 overexpression partially reversed the inhibitory effects of SMO knockdown on AR signaling activity and AR expression in LNCaP and C4-2B cells.

Conclusion: These results demonstrate that SMO loss is a characteristic of NEPC and that detecting SMO by IHC could aid pathologists in NEPC diagnosis. SMO loss may promote NEPC pathogenesis by modulating AR signaling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pros.24122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251989PMC
June 2021

A 24-bp indel within the sheep gene is associated with litter size.

Anim Biotechnol 2021 May 4:1-6. Epub 2021 May 4.

Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, China.

Aryl Hydrocarbon Receptor (AHR) is a member of the PER-ARNT-SIM (PAS) family, which could mediate various biological processes, for instance, the balance of the immune system, cell proliferation, differentiation, vascular tissue remodeling and reproduction ability regulation. A previous research showed that the gene exerted important functions on the pig reproduction, implying that it could serve as a candidate gene related to animal reproductive traits. Here, the aim of this work was to identify potential insertion/deletion (indel) mutations of the gene in three sheep breeds and analyze the associations between these mutations and reproductive traits. Results showed that a 24-bp indel was uncovered three genotypes (II, ID and DD) in the Australian White sheep (AuW) and Lanzhou fat-tail sheep (LZFT) population, while there were only two genotypes (ID and DD) in Luxi black-headed sheep (LXBH). Moreover, the Fisher's exact test showed that the 24-bp indel mutation was significantly associated with litter size and live litter size in AuW sheep (Fisher's  < 0.05). Therefore, the 24-bp indel of sheep gene can contribute to sheep marker-assisted selection breeding and further improve the sheep reproductive performance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10495398.2021.1914071DOI Listing
May 2021

Pupae Efficiently Produce Recombinant AAV2/HBoV1 Vectors with a Nuclear Polyhedrosis Virus Expression System.

Viruses 2021 04 18;13(4). Epub 2021 Apr 18.

School of Life Sciences, Jiangsu University, Zhenjiang 212013, China.

Recombinant adeno-associated virus (AAV) vectors have broad application prospects in the field of gene therapy. The establishment of low-cost and large-scale manufacturing is now the general agenda for industry. The baculovirus-insect cell/larva expression system has great potential for these applications due to its scalability and predictable biosafety. To establish a more efficient production system, pupae were used as a new platform and infected with recombinant nuclear polyhedrosis virus (BmNPV). The production of a chimeric recombinant adeno-associated virus (rAAV) serotype 2/human bocavirus type-1 (HBoV1) vector was used to evaluate the efficiency of this new baculovirus expression vector (BEV)-insect expression system. For this purpose, we constructed two recombinant BmNPVs, which were named rBmNPV/AAV2Rep-HBoV1Cap and rBmNPV/AAV2ITR-eGFP. The yields of rAAV2/HBoV1 derived from the rBmNPV/AAV2Rep-HBoV1Cap and rBmNPV/AAV2ITR-eGFP co-infected BmN cells exceeded 2 × 10 vector genomes (VG) per cell. The rBmNPV/AAV2Rep-HBoV1Cap and rBmNPV/AAV2ITR-eGFP can express stably for at least five passages. Significantly, rAAV2/HBoV1 could be efficiently generated from BmNPV-infected silkworm larvae and pupae at average yields of 2.52 × 10 VG/larva and 4.6 × 10 VG/pupa, respectively. However, the vectors produced from the larvae and pupae had a high percentage of empty particles, which suggests that further optimization is required for this platform in the future. Our work shows that silkworm pupae, as an efficient bioreactor, have great potential for application in the production of gene therapy vectors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/v13040704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073075PMC
April 2021

Inhibition of Estrogen-Related Receptor α Blocks Liver Steatosis and Steatohepatitis and Attenuates Triglyceride Biosynthesis.

Am J Pathol 2021 07 22;191(7):1240-1254. Epub 2021 Apr 22.

Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California; Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California. Electronic address:

The estrogen-related receptor (ERR) family of orphan nuclear receptors are transcriptional activators for genes involved in mitochondrial bioenergetics and metabolism. The goal of this study was to explore the role of ERRα in lipid metabolism and the potential effect of inhibiting ERRα on the development of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). In the current study, three experimental mouse models: high-fat diet, high-carbohydrate diet, and a genetic model of hepatic insulin resistance where the liver hyperinsulinemia signal is mimicked via hepatic deletion of Pten (phosphatase and tensin homolog deleted on chromosome 10), the negative regulator of the insulin/phosphatidylinositol 3-kinase signaling pathway, were used. A recently developed small-molecule inhibitor for ERRα was used to demonstrate that inhibiting ERRα blocked NAFLD development induced by either high-carbohydrate diet or high-fat diet feeding. ERRα inhibition also diminished lipid accumulation and attenuated NASH development in the Pten null mice. Glycerolipid synthesis was discovered as an additional mechanism for ERRα-regulated NAFLD/NASH development and glycerophosphate acyltransferase 4 was identified as a novel transcriptional target of ERRα. In summary, these results establish ERRα as a major transcriptional regulator of lipid biosynthesis in addition to its characterized primary function as a regulator for mitochondrial function. This study recognizes ERRα as a potential target for NAFLD/NASH treatment and elucidates novel signaling pathways regulated by ERRα.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajpath.2021.04.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261472PMC
July 2021

Adipose Tissue-derived Microvascular Fragments as Vascularization Units for Dental Pulp Regeneration.

J Endod 2021 Jul 19;47(7):1092-1100. Epub 2021 Apr 19.

National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China. Electronic address:

Introduction: The transplantation of dental pulp stem cells (DPSCs) has emerged as a novel strategy for the regeneration of lost dental pulp after pulpitis and trauma. Dental pulp regeneration of the young permanent tooth with a wide tooth apical foramen has achieved significant progress in the clinical trials. However, because of the narrow apical foramen, dental pulp regeneration in adult teeth using stem cells remains difficult in the clinic. Finding out how to promote vascular reconstitution is essential for the survival of stem cells and the regeneration of dental pulp after transplantation into the adult tooth.

Methods: Adipose tissue-derived microvascular fragments (ad-MVFs) were isolated from human adipose tissues. The apoptosis and senescence of DPSCs cultured in conditioned media were evaluated to explore the effects of ad-MVFs on DPSCs. DPSCs combined with ad-MVFs were inserted into the human tooth root segments and implanted subcutaneously into immunodeficient mice. Regenerated pulplike tissues were analyzed by hematoxylin and eosin and immunohistochemistry. The vessels in regenerated tissues were analyzed by Micro-CT and immunofluorescence.

Results: The isolated ad-MVFs contained endothelial cells and pericytes. ad-MVFs effectively prevented the apoptosis and senescence of the transplanted DPSCs both in vivo and in vitro. Combined with DPSCs, ad-MVFs obviously facilitated the formation of vascular networks in the transplants. DPSCs combined with ad-MVFs formed dental pulp-like tissues with abundant cells and matrix after 4 weeks of implantation. The supplementation of ad-MVFs led to more odontoblastlike cells and increased the formation of mineralized substance around the root canal.

Conclusions: Cotransplantation with ad-MVFs promotes the angiogenesis and revascularization of transplanted DPSC aggregates, leading to robust regeneration of dental pulp.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.joen.2021.04.012DOI Listing
July 2021

Sparse angle CT reconstruction with weighted dictionary learning algorithm based on adaptive group-sparsity regularization.

J Xray Sci Technol 2021 ;29(3):435-452

School of Artificial Intelligence and Big Data, Henan University of Technology, Zhengzhou, Henan, China.

Objective: In order to solve the blurred structural details and over-smoothing effects in sparse representation dictionary learning reconstruction algorithm, this study aims to test sparse angle CT reconstruction with weighted dictionary learning algorithm based on adaptive Group-Sparsity Regularization (AGSR-SART).

Methods: First, a new similarity measure is defined in which Covariance is introduced into Euclidean distance, Non-local image patches are adaptively divided into groups of different sizes as the basic unit of sparse representation. Second, the weight factor of the regular constraint terms is designed through the residuals represented by the dictionary, so that the algorithm takes different smoothing effects on different regions of the image during the iterative process. The sparse reconstructed image is modified according to the difference between the estimated value and the intermediate image. Last, The SBI (Split Bregman Iteration) iterative algorithm is used to solve the objective function. An abdominal image, a pelvic image and a thoracic image are employed to evaluate performance of the proposed method.

Results: In terms of quantitative evaluations, experimental results show that new algorithm yields PSNR of 48.20, the maximum SSIM of 99.06% and the minimum MAE of 0.0028.

Conclusions: This study demonstrates that new algorithm can better preserve structural details in reconstructed CT images. It eliminates the effect of excessive smoothing in sparse angle reconstruction, enhances the sparseness and non-local self-similarity of the image, and thus it is superior to several existing reconstruction algorithms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/XST-210839DOI Listing
January 2021

An analysis of Ki-67 expression in stage 1 invasive ductal breast carcinoma using apparent diffusion coefficient histograms.

Quant Imaging Med Surg 2021 Apr;11(4):1518-1531

Department of Ultrasound, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: To investigate the value of apparent diffusion coefficient (ADC) histograms in differentiating Ki-67 expression in T1 stage invasive ductal breast carcinoma (IDC).

Methods: The records of 111 patients with pathologically confirmed T1 stage IDC who underwent magnetic resonance imaging prior to surgery were retrospectively reviewed. The expression of Ki-67 in tumor tissue samples from the patients was assessed using immunohistochemical (IHC) staining, with a cut-off value of 25% for high Ki-67 labeling index (LI). ADC images of the maximum lay of tumors were selected, and the region of interest (ROI) of each lay was delineated using the MaZda software and analyzed by histogram. The correlations between the histogram characteristic parameters and the Ki-67 LI were investigated. Additionally, the histogram characteristic parameters of the high Ki-67 group (n=54) and the low Ki-67 group (n=57) were statistically analyzed to determine the characteristic parameters with significant difference. Receiver operator characteristic (ROC) analyses were further performed for the significant parameters.

Results: The mean value, and the 1st, 10th, 50th, 90th, and 99th percentiles were found to be negatively correlated with the expression of Ki-67 (all P values <0.001), with a correlation coefficient of -0.624, -0.749, -0.717, -0.621, -0.500, and -0.410, respectively. In the high Ki-67 group, the mean value, and the 1st, 10th, 50th, 90th, and 99th percentiles extracted by the histogram were significantly lower (all P values <0.05) than that of the low Ki-67 group, with areas under the ROC curves ranging from 0.717-0.856. However, the variance, skewness, and kurtosis did not differ between the two groups (all P values >0.05).

Conclusions: Histogram-derived parameters for ADC images can serve as a reliable tool in the prediction of Ki-67 proliferation status in patients with T1 stage IDC. Among the significant ADC histogram values, the 1st and 10th percentiles showed the best predictive values.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/qims-20-615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930667PMC
April 2021

Bispecific c-Met/PD-L1 CAR-T Cells Have Enhanced Therapeutic Effects on Hepatocellular Carcinoma.

Front Oncol 2021 10;11:546586. Epub 2021 Mar 10.

Department of Gastroenterology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.

T cells expressing chimeric antigen receptors, especially CD19 CAR-T cells have exhibited effective antitumor activities in B cell malignancies, but due to several factors such as antigen escape effects and tumor microenvironment, their curative potential in hepatocellular carcinoma has not been encouraging. To reduce the antigen escape risk of hepatocellular carcinoma, this study was to design and construct a bispecific CAR targeting c-Met and PD-L1. c-Met/PD-L1 CAR-T cells were obtained by lentiviral transfection, and the transfection efficiency was monitored by flow cytometry analysis. LDH release assays were used to elucidate the efficacy of c-Met/PD-L1 CAR-T cells on hepatocellular carcinoma cells. In addition, xenograft models bearing human hepatocellular carcinoma were constructed to detect the antitumor effect of c-Met/PD-L1 CAR-T cells . The results shown that this bispecific CAR was manufactured successfully, T cells modified with this bispecific CAR demonstrated improved antitumor activities against c-Met and PD-L1 positive hepatocellular carcinoma cells when compared with those of monovalent c-Met CAR-T cells or PD-L1 CAR-T cells but shown no distinct cytotoxicity on hepatocytes . experiments shown that c-Met/PD-L1 CAR-T cells significantly inhibited tumor growth and improve survival persistence compared with other groups. These results suggested that the design of single-chain, bi-specific c-Met/PD-L1 CAR-T is more effective than that of monovalent c-Met CAR-T for the treatment of hepatocellular carcinoma., and this bi-specific c-Met/PD-L1 CAR is rational and implementable with current T-cell engineering technology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.546586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987916PMC
March 2021
-->