Publications by authors named "Tao Zhang"

4,613 Publications

  • Page 1 of 1

Developmental neurotoxicity of antimony (Sb) in the early life stages of zebrafish.

Ecotoxicol Environ Saf 2021 May 8;218:112308. Epub 2021 May 8.

Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400030, China. Electronic address:

Accumulating studies have revealed the toxicity of antimony (Sb) to soil-dwelling and aquatic organisms at the individual level. However, little is known about the neurotoxic effects of antimony and its underlying mechanisms. To assess this issue, we investigated the neurotoxicity of antimony (0, 200, 400, 600 and 800 mg/L) in zebrafish embryos. After exposure, zebrafish embryos showed abnormal phenotypes such as a shortened body length, morphological malformations, and weakened heart function. Behavioral experiments indicated that antimony caused neurotoxicity in zebrafish embryos, manifested in a decreased spontaneous movement frequency, delayed response to touch, and reduced movement distance. We also showed that antimony caused a decrease in acetylcholinesterase (AChE) levels in zebrafish embryos, along with decreased expression of neurofunctional markers such as gfap, nestin, mbp, and shha. Additionally, antimony significantly increased reactive oxygen species levels and significantly reduced glutathione (GSH) and superoxide dismutase (SOD) activity. In summary, our findings indicated that antimony can induce developmental toxicity and neurotoxicity in zebrafish embryos by affecting neurotransmitter systems and oxidative stress, thus altering behavior. These outcomes will advance our understanding of antimony-induced neurotoxicity, environmental problems, and health hazards.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ecoenv.2021.112308DOI Listing
May 2021

Oxidation of Pd(II) with disilane in a palladium-catalyzed disilylation of aryl halides: a theoretical view.

Dalton Trans 2021 May 11. Epub 2021 May 11.

School of Chemistry and Chemical Engineering, and Chongqing Key Laboratory of Theoretical and Computational Chemistry, Chongqing University, Chongqing 400030, P. R. China. and Green Catalysis Center, and College of Chemistry Zhengzhou University Zhengzhou, Henan 450001, China.

Density functional theory (DFT) calculation has been used to reveal the mechanism of the Pd-catalyzed disilylation reaction of aryl halides. The DFT calculations indicate that the reaction starts with the oxidative addition of the C-I bond to the Pd(0) catalyst. Concerted metalation-deprotonation (CMD) can then generate a five-membered palladacycle. Insertion of Pd(ii) into the Si-Si bond in disilane followed by two sequential steps of reductive eliminations yields the disilylation product and regenerates the Pd(0) catalyst. According to the NPA charge analysis along the reaction coordinates, the formal oxidative addition of the Si-Si bond to palladium could be considered as the insertion of palladium into the Si-Si bond. However, the conventional oxidative addition of the C-I bond to palladium is exactly an oxidation process with the electron transfer from the palladium atom to the C-I bond. Therefore, electron rich Pd(0) is beneficial for the oxidation process, and Pd(ii) prone to acquire electrons is beneficial for the insertion process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1dt00399bDOI Listing
May 2021

Toxicity of quantum dots on target organs and immune system.

J Appl Toxicol 2021 May 10. Epub 2021 May 10.

Key Laboratory of Environmental Medicine & Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China.

Quantum dots (QDs), due to their superior luminous properties, have been proven to be a very promising biological probe, which can be used as a candidate material for clinical applications. The toxicity of QDs in the environment and biological systems has caused widespread concern in the nanosphere, but their immune toxicity and their impact on the immune system are still relatively unknown. At present, the research on the toxicity of QDs is mainly focused on in vitro models, but few have systematically evaluated their adverse effects on target organs. Animal studies have shown that QDs can be accumulated in various organs due to their main exposure routes, thereby posing a potential threat to major organs. This review briefly describes general characteristics and the wide medical applications of QDs and focuses on the adverse effects of QDs on major target organs, such as liver, lung, kidney, brain, and spleen, after acute and chronic exposure. QDs mainly cause changes in the corresponding indicators of target organs, such as oxidative damage, and in severe cases cause hyperemia, tissue necrosis, and even death. In addition to causing direct damage to target organs, QDs can also cause a large number of immune cells to accumulate and cause inflammatory reactions when causing damage to other major organs. Whether it is to avoid the risk of people contacting QDs in production and life, or to realize the clinical applications of QDs, is very essential to conduct systematic in vivo toxicity assessment of QDs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jat.4180DOI Listing
May 2021

Destroying the structure of extracellular polymeric substance to improve the dewatering performance of waste activated sludge by ionic liquid.

Water Res 2021 Apr 17;199:117161. Epub 2021 Apr 17.

Sichuan Base of International Science and Technology Cooperation for Green Chemical Industry, School of Chemical Engineering, Sichuan University, Chengdu, 610065, China. Electronic address:

The disposal and resource utilization of waste activated sludge (WAS) is a big challenge for its high moisture content. Ionic liquid (IL), 1-ethyl-3-methylimidazolium trifluoromethanesulfonate ([EMIM][OTf]), was innovatively used as a conditioner to improve the dewatering performance of WAS. The WAS was characterized by flocs size, three-dimensional excitation-emission matrix (3D-EEM), zeta potential, Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscope (SEM) for the investigation of intensification mechanism. The results showed that the dewatering performance of WAS conditioned by [EMIM][OTf] was significantly improved. The moisture content was successfully decreased to 64.99±0.92 %, and the intensification mechanism was investigated. The results showed that the structures of extracellular polymeric substance (EPS) were destroyed by [EMIM][OTf]. It brought a sharp decrease of the contents of polysaccharides (PS), proteins (PN), humic acid (HA) and fulvic acid (FA) in tightly bound extracellular polymeric substance (TB-EPS) structure. The inactivation of microbial cells promoted the disintegration of flocs. Large flocs were converted into unstable small particles and biopolymers. In addition, the negative charges of WAS were also neutralized for dissolution of biopolymers in [EMIM][OTf], and the electrostatic repulsion between flocs was weakened. [EMIM][OTf] was easily recycled five times. The research results indicate that specific IL, such as [EMIM][OTf], is a potential conditioner to improve the dewatering performance of WAS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.watres.2021.117161DOI Listing
April 2021

Ni-Catalyzed Dual C-H Annulation of Benzimidazoles with Alkynes for Synthesis of π-Extended Heteroarenes.

Org Lett 2021 May 10. Epub 2021 May 10.

State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.

Transition metal catalyzed dual C-H activation and annulation with alkynes was an attractive protocol to construct polycyclic π-extended structures. However, most of them were dominated by noble metal catalysts. Disclosed herein was the study of base-metal Ni-catalysis for dual C-H annulation of -aromatic imidazole, which produced a range of desired polycyclic aza-quinolines in 48-95% yields. The use of bifunctional phosphine oxide ligand proved to be critical for success.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.1c01253DOI Listing
May 2021

Atypia in pulmonary cytology: A cytomorphometric analysis of the spectrum of changes between benign and malignant.

Diagn Cytopathol 2021 May 10. Epub 2021 May 10.

Department of Pathology and Laboratory Medicine, ARUP Laboratories, Salt Lake City, Utah, USA.

Background: Cytopathologists reviewing pulmonary specimens are expected to classify samples into clinically useful categories. Clinicians prefer reports to convey a definitively benign or definitively malignant diagnosis. Cytopathologists recognize a spectrum of morphologic features with increasing degrees of atypia between clearly benign and clearly malignant. A variety of terms are used to convey to clinicians how concerned a cytologist is that a malignancy maybe present. These terms include "atypia", "atypical" and "suspicious for malignancy", but have had variable meanings among cytopathologists and clinicians. Categorization schemes have been proffered to include standardization of terminology with many of these systems containing one or more intermediate categories.

Methods: An electronic search of the University of Missouri cytology reporting system was made for all bronchial brushings specimens diagnosed using the Papanicolaou Society of Cytopathology System for Reporting Respiratory Cytology (PSCSR) between January 2019 and December 2019. Slides were reviewed to determine adequate cellularity and preparation quality. From those found to be adequately cellular and of good quality, four bronchial brushing specimens from each PSCSR category were randomly selected. For each case a slide was digitized and at least 70 of the most "atypical" cells were analyzed by the Aperio System for nuclear area and nuclear/cytoplasmic ratio. Distribution of measured parameters among categories was analyzed by the Kruskal-Wallis test.

Results: During the study period, only the PSCSR categories "benign", "atypical" and "malignant" were recorded. A significant difference in distribution of nuclear/cytoplasmic ratio was seen between the "benign" and "atypical" categories but not between the "atypical" and "malignant" categories. The "atypical" category appeared to be bi-modal indicating that it could be divided into two categories, "atypical" and "suspicious for malignancy".

Conclusions: The categories "atypical" and "suspicious for malignancy" served to divide the spectrum of cytomorphologic changes between "benign" and "malignant" into clinically useful groups. The use of these categories is supported by cytomorphometric analysis of bronchial brushing specimens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/dc.24769DOI Listing
May 2021

I Seed Promotes Apoptosis in Non-small Lung Cancer Cells the p38 MAPK-MDM2-p53 Signaling Pathway.

Front Oncol 2021 21;11:582511. Epub 2021 Apr 21.

Department of Radiology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China.

I seeds were effective in the treatment of non-small cell lung cancer in previous research. However, the exact signaling pathway-mediated apoptosis mechanism is still unclear. The present study analyzed the effects and potential mechanisms of I seed on the growth and migration of A549 cells. Lung cancer A549 cells were irradiated with I seed for various times. MTT, invasion assay, and flow cytometry were used to detect the proliferation, invasion, and apoptosis of treated cells, respectively. A Nimblegen genome-wide expression profile chip was used to evaluate gene expression changes in I seed-treated A549 cells. Validation studies were performed using phosphorylated protein chip technology, Western blot, nude mouse tumor xenograft assay, and immunohistochemical experiments. All statistical analyses were performed using unpaired Student's tests and Kruskal-Wallis test. Irradiation with I seed inhibited A549 cell proliferation and invasion and induced apoptosis (primarily early apoptosis). Irradiation with I seed also caused the downregulation of p38MAPK, degradation of mouse double-minute 2 homolog (MDM2), and higher expression of p53, which eventually resulted in non-small cell lung cancer cell apoptosis. I seed irradiation activated the p38MAPK/MDM2/p53 signaling pathway and promoted non-small cell lung cancer cell apoptosis. Future clinical studies targeting this signal may provide a new potential therapeutic approach for non-small cell lung cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.582511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096899PMC
April 2021

Xi Lei San Attenuates Dextran Sulfate Sodium-Induced Colitis in Rats and TNF--Stimulated Colitis in CACO2 Cells: Involvement of the NLRP3 Inflammasome and Autophagy.

Mediators Inflamm 2021 21;2021:1610251. Epub 2021 Apr 21.

Department of Urology, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, Sichuan Province, China.

Objective: Inflammatory bowel disease (IBD) is a chronic nonspecific inflammatory bowel disease with an unclear etiology. The active ingredients of traditional Chinese medicines (TCMs) exert anti-inflammatory, antitumor, and immunomodulatory effects, and their multitarget characteristics provide them with a unique advantage for treating IBD. However, the therapeutic effects and underlying mechanisms of Xi Lei San in treatment of IBD remain unknown. This study was designed to investigate whether Xi Lei San exerted an anti-inflammatory effect in IBD via a mechanism involving NLRP3 inflammasomes and autophagy.

Methods: We successfully established a rat model of dextran sulfate sodium- (DSS-) induced colitis as well as a cellular model of TNF--induced colitis. Xi Lei San and indirubin were identified by HPLC analysis. Rats were treated with Xi Lei San or alum crystals, and their body weights and morphology of intestinal tissues were examined. A western blot analysis was performed to determine the expression levels of inflammasome-related proteins and autophagy-related proteins, ELISA was performed to analyze IL-1, IL-18, and IL-33 concentrations, and flow cytometry was used to monitor cell apoptosis and ROS levels.

Results: Xi Lei San and indirubin were identified by HPLC analysis. We found that Xi Lei San could significantly increase the weights of rats and improve the structure of the intestinal tissues in DSS-induced colitis model rats. We also found that Xi Lei San significantly inhibited NLRP3 inflammasome activity, reduced the levels of inflammatory cytokines, and suppressed autophagy in DSS-induced colitis model rats. experiments revealed that Xi Lei San could repress apoptosis as well as ROS and inflammatory cytokine production in TNF--induced CACO2 cells by reducing the activity of NLRP3 inflammasomes and autophagy.

Conclusions: Our findings showed that Xi Lei San significantly ameliorated IBD by inhibiting NLRP3 inflammasome, autophagy, and oxidative stress.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/1610251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084655PMC
April 2021

Reduction-responsive Dehydroepiandrosterone Prodrug Nanoparticles Loaded with Camptothecin for Cancer Therapy by Enhancing Oxidation Therapy and Cell Replication Inhibition.

Int J Pharm 2021 May 4:120671. Epub 2021 May 4.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China. Electronic address:

The pentose phosphate pathway (PPP) plays a critical role by providing ribulose-5-phosphate (Ru5P) and NADPH for nucleotide synthesis and reduction energy, respectively. Accordingly, blocking the PPP process may be an effective strategy for enhancing oxidation therapy and inhibiting cell replication. Here, we designed a novel reduction-responsive PEGylated prodrug and constructed nanoparticles PsD@CPT to simultaneously deliver a PPP blocker, dehydroepiandrosterone (DHEA), and chemotherapeutic camptothecin (CPT) to integrate amplification of oxidation therapy and enhance cell replication inhibition. Following cellular uptake, DHEA and CPT were released from PsD@CPT in the presence of high glutathione (GSH) levels. As expected, DHEA-mediated reduction level decreases and CPT-induced oxidation level increases synergistically, breaking the redox balance to aggravate cancer oxidative stress. In addition, suppressing nucleotide synthesis by DHEA through the reduction of Ru5P and blocking DNA replication by CPT further motivates a synergistic inhibition effect on tumor cell proliferation. The results showed that PsD@CPT featuring multimodal treatment has satisfactory antitumor activity both in vitro and in vivo. This study provides a new tumor treatment strategy, which combines the amplification of oxidative stress and enhancement of inhibition of cell proliferation based on inhibition of the PPP process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpharm.2021.120671DOI Listing
May 2021

Chorus2: design of genome-scale oligonucleotide-based probes for fluorescence in situ hybridization.

Plant Biotechnol J 2021 May 7. Epub 2021 May 7.

Department of Plant Biology, Michigan State University, East Lansing, MI, 48824, USA.

Oligonucleotide (oligo)-fluorescence in situ hybridization (FISH) has rapidly becoming the new generation of FISH technique in plant molecular cytogenetics research. Genome-scale identification of single copy oligos is the foundation of successful oligo-FISH experiments. Here, we introduce Chorus2, a software that is developed specifically for oligo selection. We demonstrate that Chorus2 is highly effective to remove all repetitive elements in selection of single copy oligos, which is critical for the development of successful FISH probes. Chorus2 is more effective than Chorus, the original version of the pipeline, and OligoMiner for repeat removal. Chorus2 allows to select oligos that are conserved among related species, which extends the usage of oligo-FISH probes among phylogenetically related plant species. We also implemented a new function in Chorus2 that allows development of FISH probes from plant species without an assembled genome. We anticipate that Chorus2 can be used in plants as well as in mammalian and other non-plant species. Chorus2 will broadly facilitate the design of FISH probes for various types of application in molecular cytogenetics research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pbi.13610DOI Listing
May 2021

POSTN Promotes the Proliferation of Spermatogonial Cells by Activating the Wnt/β-Catenin Signaling Pathway.

Reprod Sci 2021 May 6. Epub 2021 May 6.

Department of Stem Cells and Regenerative Medicine, Shenyang Key Laboratory of Stem Cell and Regenerative Medicine, China Medical University, Shenyang, 110013, Liaoning, China.

The self-renewal of spermatogonial cells (SCs) provides the foundation for life-long spermatogenesis. To date, only a few growth factors have been used for the culture of SCs in vitro, and how to enhance proliferation capacity of SCs in vitro needs further research. This study aimed to explore the effects of periostin (POSTN) on the proliferation of human SCs. GC-1 spg cells were cultured in a medium with POSTN, cell proliferation was evaluated by MTS analysis and EdU assay, and the Wnt/β-catenin signaling pathway was examined. Thereafter, the proliferations of human SC were detected using immunofluorescence and RT-PCR. In this study, we found that CM secreted by human amniotic mesenchymal stem cells (hAMSCs) could enhance the proliferation capacity of mouse GC-1 spg cells. Label-free mass spectrometry and ELISA analysis demonstrated that high level of POSTN was secreted by hAMSCs. MTS and EdU staining showed that POSTN increased GC-1 spg cell proliferation, whereas CM from POSTN-silenced hAMSCs suppressed cell proliferation capacity. Then POSTN was found to activate the Wnt/β-catenin signaling pathway to regulate the proliferation of GC-1 spg cells. XAV-939, a Wnt/β-catenin inhibitor, partially reversed the effects of POSTN on GC-1 spg cell proliferation. We then analyzed human SCs and found that POSTN promoted human SC proliferation in vitro. These findings provide insights regarding the role of POSTN in regulating SC proliferation via the Wnt/β-catenin signaling pathway and suggest that POSTN may serve as a cytokine for male infertility therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s43032-021-00596-1DOI Listing
May 2021

Natural allelic variation in a modulator of auxin homeostasis improves grain yield and nitrogen use efficiency in rice.

Plant Cell 2021 May;33(3):566-580

State Key Laboratory of Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, Nanjing 210095, China.

The external application of nitrogen (N) fertilizers is an important practice for increasing crop production. However, the excessive use of fertilizers significantly increases production costs and causes environmental problems, making the improvement of crop N-use efficiency (NUE) crucial for sustainable agriculture in the future. Here we show that the rice (Oryza sativa) NUE quantitative trait locus DULL NITROGEN RESPONSE1 (qDNR1), which is involved in auxin homeostasis, reflects the differences in nitrate (NO3-) uptake, N assimilation, and yield enhancement between indica and japonica rice varieties. Rice plants carrying the DNR1indica allele exhibit reduced N-responsive transcription and protein abundance of DNR1. This, in turn, promotes auxin biosynthesis, thereby inducing AUXIN RESPONSE FACTOR-mediated activation of NO3- transporter and N-metabolism genes, resulting in improved NUE and grain yield. We also show that a loss-of-function mutation at the DNR1 locus is associated with increased N uptake and assimilation, resulting in improved rice yield under moderate levels of N fertilizer input. Therefore, modulating the DNR1-mediated auxin response represents a promising strategy for achieving environmentally sustainable improvements in rice yield.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/plcell/koaa037DOI Listing
May 2021

Identification of a novel glycolysis-related gene signature for predicting the prognosis of osteosarcoma patients.

Aging (Albany NY) 2021 May 5;13. Epub 2021 May 5.

Department of Orthopedics, Shanghai Bone Tumor Institution, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China.

Glycolysis ensures energy supply to cancer cells, thereby facilitating tumor progression. Here, we identified glycolysis-related genes that could predict the prognosis of patients with osteosarcoma. We examined 198 glycolysis-related genes that showed differential expression in metastatic and non-metastatic osteosarcoma samples in the TARGET database, and identified three genes (P4HA1, ABCB6, and STC2) for the establishment of a risk signature. Based on the signature, patients in the high-risk group had poor outcomes. An independent Gene Expression Omnibus database GSE21257 was selected as the validation cohort. Receiver operating characteristic curve analysis was performed and the accuracy of predicting the 1- and 3-year survival rates was shown by the areas under the curve. The results were 0.884 and 0.790 in the TARGET database, and 0.740 and 0.759 in the GSE21257, respectively. Furthermore, we applied ESTIMATE algorithm and performed single sample gene set enrichment analysis to compare tumor immunity between high- and low-risk groups. We found that the low-risk group had higher immune scores and immune infiltration levels than the high-risk group. Finally, we chose P4HA1 as a representative gene to verify the function of risk genes and and found that P4HA1 could promote the metastasis of osteosarcoma cells. Our study established a novel glycolysis-related risk signature that could predict the prognosis of patients with osteosarcoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.202958DOI Listing
May 2021

PHF8-promoted TOPBP1 demethylation drives ATR activation and preserves genome stability.

Sci Adv 2021 May 5;7(19). Epub 2021 May 5.

State Key Laboratory of Experimental Hematology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin 300070, China.

The checkpoint kinase ATR [ATM (ataxia-telangiectasia mutated) and rad3-related] is a master regulator of DNA damage response. Yet, how ATR activity is regulated remains to be investigated. We report here that histone demethylase PHF8 (plant homeodomain finger protein 8) plays a key role in ATR activation and replication stress response. Mechanistically, PHF8 interacts with and demethylates TOPBP1 (DNA topoisomerase 2-binding protein 1), an essential allosteric activator of ATR, under unperturbed conditions, but replication stress results in PHF8 phosphorylation and dissociation from TOPBP1. Consequently, hypomethylated TOPBP1 facilitates RAD9 (RADiation sensitive 9) binding and chromatin loading of the TOPBP1-RAD9 complex to fully activate ATR and thus safeguard the genome and protect cells against replication stress. Our study uncovers a demethylation and phosphorylation code that controls the assembly of TOPBP1-scaffolded protein complex, and provides molecular insight into non-histone methylation switch in ATR activation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/sciadv.abf7684DOI Listing
May 2021

Concurrent chemoradiotherapy versus radiotherapy alone for patients with locally advanced esophageal squamous cell carcinoma in the era of intensity modulated radiotherapy: a propensity score-matched analysis.

Thorac Cancer 2021 May 5. Epub 2021 May 5.

Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: To investigate the survival benefit of concurrent chemoradiotherapy (CCRT) for patients with locally advanced esophageal squamous cell carcinoma (ESCC) during the years of intensity-modulated radiotherapy (IMRT).

Methods: Medical records of 1089 patients with ESCC who received IMRT from January 2005 to December 2017 were retrospectively reviewed. A total of 617 patients received CCRT, 472 patients received radiotherapy (RT) alone. Propensity score matching (PSM) method was used to eliminate baseline differences between the two groups. Survival and toxicity profile were evaluated afterward.

Results: After a median follow-up time of 47.9 months (3.2-149.8 months), both overall survival (OS) and progression-free survival (PFS) of the CCRT group were better than those of the RT alone group, either before or after PSM. After PSM, the 1-, 3-, and 5-year OS of RT alone and CCRT groups were 59.0% versus 70.2%, 27.7% versus 40.5% and 20.3% versus 33.1%, respectively (p < 0.001). The 1-, 3-, and 5-year PFS were 39.4% versus 49.0%, 18.3% versus 30.4% and 10.5% versus 25.0%, respectively (p < 0.001). The rates of ≥ grade 3 leukopenia and radiation esophagitis in the CCRT group were higher than that of RT alone group (p < 0.05). There was no significant difference in the probability of radiation pneumonitis between the two groups (p = 0.167). Multivariate Cox analysis indicated that female, EQD2 ≥60 Gy and concurrent chemotherapy were favorable prognostic factors for both OS and PFS.

Conclusions: Concurrent chemotherapy can bring survival benefits to patients with locally advanced ESCC receiving IMRT. For patients who cannot tolerate concurrent chemotherapy, RT alone is an effective alternative with promising results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1759-7714.13971DOI Listing
May 2021

Pharmaceuticals targeting signaling pathways of endometriosis as potential new medical treatment: A review.

Med Res Rev 2021 May 5. Epub 2021 May 5.

Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong.

Endometriosis (EM) is defined as endometrial tissues found outside the uterus. Growth and development of endometriotic cells in ectopic sites can be promoted via multiple pathways, including MAPK/MEK/ERK, PI3K/Akt/mTOR, NF-κB, Rho/ROCK, reactive oxidative stress, tumor necrosis factor, transforming growth factor-β, Wnt/β-catenin, vascular endothelial growth factor, estrogen, and cytokines. The underlying pathophysiological mechanisms include proliferation, apoptosis, autophagy, migration, invasion, fibrosis, angiogenesis, oxidative stress, inflammation, and immune escape. Current medical treatments for EM are mainly hormonal and symptomatic, and thus the development of new, effective, and safe pharmaceuticals targeting specific molecular and signaling pathways is needed. Here, we systematically reviewed the literature focused on pharmaceuticals that specifically target the molecular and signaling pathways involved in the pathophysiology of EM. Potential drug targets, their upstream and downstream molecules with key aberrant signaling, and the regulatory mechanisms promoting the growth and development of endometriotic cells and tissues were discussed. Hormonal pharmaceuticals, including melatonin, exerts proapoptotic via regulating matrix metallopeptidase activity while nonhormonal pharmaceutical sorafenib exerts antiproliferative effect via MAPK/ERK pathway and antiangiogenesis activity via VEGF/VEGFR pathway. N-acetyl cysteine, curcumin, and ginsenoside exert antioxidant and anti-inflammatory effects via radical scavenging activity. Natural products have high efficacy with minimal side effects; for example, resveratrol and epigallocatechin gallate have multiple targets and provide synergistic efficacy to resolve the complexity of the pathophysiology of EM, showing promising efficacy in treating EM. Although new medical treatments are currently being developed, more detailed pharmacological studies and large sample size clinical trials are needed to confirm the efficacy and safety of these treatments in the near future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/med.21802DOI Listing
May 2021

Mitochondria-targeted high-load sound-sensitive micelles for sonodynamic therapy to treat triple-negative breast cancer and inhibit metastasis.

Mater Sci Eng C Mater Biol Appl 2021 May 25;124:112054. Epub 2021 Mar 25.

School of Life Science, Institute of Engineering Medicine, Beijing Institute of Technology, Beijing 100081, China. Electronic address:

Breast cancer is the most common cancer among women worldwide, of which 10-20% accounts for triple-negative breast cancer (TNBC). TNBC is more aggressive, lacks an effective treatment target, and has a higher metastasis rate compared to other types of breast cancers. These characteristics result in poor therapeutic and prognostic outcomes in patients with TNBC. Sonodynamic therapy (SDT) is an emerging non-invasive procedure with high-tissue penetration properties to treat cancer. Therefore, we designed a new sonosensitizer, PEG-IR780@Ce6 for SDT, which showed excellent performance in inhibiting cancer cells and in simultaneously suppressing the migration and invasion of cancer cells. In vitro and in vivo experiments showed that PEG-IR780@Ce6 as a sonosensitizer could generate higher levels of reactive oxygen species (ROS) than IR780 and free Ce6 alone, thereby resulting in better anti-cancer effects. Besides, PEG-IR780@Ce6 inhibited the migration and invasion of MDA-MB-231 cells, both in vitro and in vivo, which indicated that it could suppress the metastasis of TNBC. Moreover, the long circulation time and the mitochondria-targeting ability of PEG-IR780@Ce6 guaranteed its accumulation in the tumor. In addition, both in vitro and in vivo experiments indicated the biocompatibility and biosafety of PEG-IR780@Ce6. In conclusion, our results collectively suggested that the newly designed sonosensitizer, PEG-IR780@Ce6, is a promising treatment option for TNBC with excellent therapeutic effects and low side effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msec.2021.112054DOI Listing
May 2021

PDGFR-β fibroblasts deteriorate survival in human solid tumors: a meta-analysis.

Aging (Albany NY) 2021 May 3;13. Epub 2021 May 3.

Department of General Surgery III, Affiliated Hospital of Shaoxing University, Zhejiang 312000, China.

Fibroblasts are a highly heterogeneous population in tumor microenvironment. PDGFR-β fibroblasts, a subpopulation of activated fibroblasts, have proven to correlate with cancer progression through multiple of mechanisms including inducing angiogenesis and immune evasion. However, the prognostic role of these cells in solid tumors is still not conclusive. Herein, we carried out a meta-analysis including 24 published studies with 6752 patients searched from PubMed, Embase and EBSCO to better comprehend the value of such subpopulation in prognosis prediction for solid tumors. We noted that elevated density of intratumoral PDGFR-β fibroblasts was remarkably associated with worse overall survival (OS) and disease-free survival (DFS) of patients. In subgroup analyses, the data showed that PDGFR-β fibroblast infiltration considerably decreased OS in non-small cell lung cancer (NSCLC), breast and pancreatic cancer, and reduced DFS in breast cancer. In addition, increased number of PDGFR-β fibroblasts appreciably correlated with advanced TNM stage of patients. In conclusion, PDGFR-β fibroblast infiltration deteriorates survival in human solid tumors especially in NSCLC, breast and pancreatic cancer. Hence, they may offer a practicable prognostic biomarker and a potential therapeutic strategy for these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.202952DOI Listing
May 2021

Simulation of gas transport in a landfill with layered new and old municipal solid waste.

Sci Rep 2021 May 3;11(1):9436. Epub 2021 May 3.

College of Hohai, Chongqing Jiaotong University, Chongqing, 400074, China.

Average biodegradation rate of newly filled municipal solid waste (MSW) in landfills is relatively fast, and the landfill gas produced by the new MSW biodegradation can cause great variations in gas pressure. To predict the gas pressure distribution in the MSW layer, a one-dimensional gas transport model is established in this study. The following factors are considered in this model: (1) the variation of gas permeability with depth; (2) the anisotropy ratio of gas permeability; (3) the settlement caused by waste biodegradation. Furthermore, a single peak model for gas production is applied as the source term of gas production. The equation for settlement caused by waste biodegradation is presented, and the time of peak gas production rate is obtained by fitting the settlement of the newly filled layer. The stratification of the unsaturated and saturated regions is taken into account by distinguishing the difference in gas saturation. The layering of the new and old waste layers is considered by distinguishing the difference in the length of time that waste has been degraded to produce gas. Based on the method of numerical calculation, the gas pressure distribution in the landfill with layered new and old MSW is well simulated. The position where the maximum gas pressure occurs is found. The sensitivity analysis shows that the influence of the anisotropy ratio on gas pressure distribution is more significant.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-88858-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093249PMC
May 2021

Leukocyte/platelet hybrid membrane-camouflaged dendritic large pore mesoporous silica nanoparticles co-loaded with photo/chemotherapeutic agents for triple negative breast cancer combination treatment.

Bioact Mater 2021 Nov 13;6(11):3865-3878. Epub 2021 Apr 13.

Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Pharmaceutics, School of Pharmacy, Tianjin Medical University, Tianjin, 300070, China.

Triple-negative breast cancer (TNBC) is an aggressive subset of breast cancer and currently lacks effective therapeutic targets. As two main phototherapeutic methods, photothermal therapy (PTT) and photodynamic therapy (PDT) show many advantages in TNBC treatment, and their combination with chemotherapy can achieve synergistic therapeutic effects. In the present study, a biomimetic nanoplatform was developed based on leukocyte/platelet hybrid membrane (LPHM) and dendritic large pore mesoporous silicon nanoparticles (DLMSNs). A near infrared (NIR) fluorescent dye IR780 and a chemotherapeutic drug doxorubicin (DOX) were co-loaded into the large pores of DLMSNs to prepare DLMSN@DOX/IR780 (DDI) nanoparticles (NPs), followed by camouflage with LPHM to obtain LPHM@DDI NPs. Through the mediation of LPHM, LPHM@DDI NPs showed an excellent TNBC-targeting ability and very high PTT/PDT performances and . Upon NIR laser irradiation, LPHM@DDI NPs exhibited synergistic cytotoxicity and apoptosis-inducing activity in TNBC cells, and effectively suppressed tumor growth and recurrence in TNBC mice through tumor ablation and anti-angiogenesis. These synergistic effects were sourced from the combination of PTT/PDT and chemotherapy. Altogether, this study offers a promising biomimetic nanoplatform for efficient co-loading and targeted delivery of photo/chemotherapeutic agents for TNBC combination treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioactmat.2021.04.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076651PMC
November 2021

Changes in left ventricular and atrial mechanics and function after dialysis in patients with end-stage renal disease.

Quant Imaging Med Surg 2021 May;11(5):1899-1908

Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: Hemodialysis (HD) can influence end-stage renal disease (ESRD) patients' circulatory system. The present study aimed to evaluate the effect of volume depletion on left ventricular (LV) and left atrial (LA) function and determine the volume-independent parameters before and after HD in patients with ESRD.

Methods: Between January 2018 and January 2019, we recruited long-term HD patients (n=40, 51.0±16.4 years), excluding those with structural cardiac disease. Echocardiographic parameters, including LV and LA volumes, flow Doppler, pulsed tissue Doppler, and speckle tracking echocardiography (STE) before and after HD (within 24 h), were examined, and the values were compared.

Results: Following HD, alteration in LV end-systolic volume was not detected, whereas LV end-diastolic volume (90.18±23.91 84.21±23.54 mL, P=0.036) and LV ejection fraction (LVEF; 64.63%±6.56% 62.84%±6.56%, P=0.049) decreased. Peak early diastolic trans-mitral flow velocity (E-wave; 82.22±20.13 72.43±18.32 cm/s, P<0.001), peak early diastolic tissue Doppler velocity (e'; 6.45±1.88 5.77±1.63 cm/s, P<0.001) at the septal side of the mitral annulus, the ratio of early to late Doppler velocities of diastolic mitral inflow (0.90±0.27 0.79±0.23, P<0.001), and the average E/e' ratio (12.54±4.08 11.28±4.52, P=0.049) decreased significantly. No significant difference was found in peak blood flow velocity at the mitral valve during late diastole and e' at the lateral side of the mitral annulus after HD. LA volume index (35.55±12.61 30.22±9.80 mL/m, P<0.001), tricuspid regurgitation velocity (260.11±36.54 242.37±32.22 cm/s, P=0.002), and pulmonary artery systolic pressure (33.63±11.29 29.94±7.80 mmHg, P=0.006) significantly decreased. LV global longitudinal systolic strain (GLS) of 4-chamber view (-24.37%±3.02% -23.38%±3.33%, P=0.019), rather than global circumferential systolic strain, exhibited significant change after HD. Significant changes were also found in LV longitudinal early diastolic strain rate (LSRe; 1.17±0.25 1.05±0.24 s, P<0.001) and early diastolic global radial velocity (Ve; 2.62±0.59 2.25±0.67 cm/s, P=0.011) after HD, but not in other strain rates and global radial velocity measurements. LA maximal volume (35.55±12.61 30.22±9.80 mL/m, P<0.001), LA total emptying fraction (54.19%±10.39% 49.63%±11.05%, P=0.009), and LA passive emptying fraction (32.23%±12.86% 26.81%±9.28%, P=0.004) decreased significantly after HD, while LA minimal volume, the volume at the onset of atrial systole, and LA active emptying fraction after HD were not significantly different.

Conclusions: Most indices of systolic (LVEF and GLS of 4-chamber view) and early diastolic function (E-wave, e', LSRe, global radial Ve, and LA passive emptying fraction) were preload dependent. Late diastolic indices, including LV late diastolic global longitudinal strain rate, late diastolic global radial velocity, and LA active emptying fraction, did not change with volume depletion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/qims-20-961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047354PMC
May 2021

Predicting compassion fatigue among psychological hotline counselors using machine learning techniques.

Curr Psychol 2021 Apr 26:1-12. Epub 2021 Apr 26.

School of Psychology, Central China Normal University, Key Laboratory of Adolescent Cyberpsychology and Behavior, Ministry of Education, Key Laboratory of Human Development and Mental Health of Hubei Province, Wuhan, China.

During the outbreak of coronavirus disease 2019, psychological hotline counselors frequently address help-seekers' traumatic experiences from time to time, which possibly causes counselors' compassion fatigue. The present study aimed to explore the predictors of compassion fatigue among a high-risk population of psychological hotline counselors. Seven hundred and twelve psychological hotline counselors were recruited from the Mental Health Service Platform at Central China Normal University, Ministry of Education, then were asked to complete the questionnaires measuring compassion fatigue, trait empathy, social support, trait mindfulness, counselor's self-efficacy, humor, life meaning, and post-traumatic growth. A chi-square test was utilized to filter for the top-20 predictive variables. Machine learning techniques, including logistic regression, decision tree, random forest, k-nearest neighbor, support vector machine, and naïve Bayes were employed to predict compassion fatigue. The results showed that the most important predictors of compassion fatigue were meaning in life, counselors' self-efficacy, mindfulness, and empathy. Except for the decision tree, the rest machine learning techniques obtained good performance. Naïve Bayes presented the highest area under the receiver operating characteristic curve of 0.803. Random forest achieved the least classification error of 23.64, followed by Naïve Bayes with a classification error of 23.85. These findings support the potential application of machine learning techniques in the prediction of compassion fatigue.

Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-021-01776-7.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12144-021-01776-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074269PMC
April 2021

Tübingen hip flexion splint more successful than Pavlik harness for decentred hips after the age of three months.

Bone Joint J 2021 May;103-B(5):991-998

Department of Pediatric Orthopaedics, Beijing Jishuitan Hospital, Beijing, China.

Aims: The objective of this study was to evaluate the clinical and radiological outcomes of patients younger than six months of age with developmental dysplasia of the hip (DDH) managed by either a Pavlik harness or Tübingen hip flexion splint.

Methods: Records of 251 consecutive infants with a mean age of 89 days (SD 47), diagnosed with DDH between January 2015 and December 2018, were retrospectively reviewed. Inclusion criteria for patients with DDH were: younger than 180 days at the time of diagnosis; ultrasound Graf classification of IIc or greater; treatment by Pavlik harness or Tübingen splint; and no prior treatment history. All patients underwent hip ultrasound every seven days during the first three weeks of treatment and subsequently every three to four weeks until completion of treatment. If no signs of improvement were found after three weeks, the Pavlik harness or Tübingen splint was discontinued. Statistical analysis was performed.

Results: The study included 251 patients with Graf grades IIc to IV in 18 males and 233 females with DDH. Mean follow-up time was 22 months (SD 10). A total of 116 hips were graded as Graf IIc (39.1%), nine as grade D (3.0%), 100 as grade III (33.7%), and 72 as grade IV (24.2%). There were 109 patients (128 hips) in the Pavlik group and 142 patients (169 hips) in the Tübingen group (p = 0.227). The Tübingen group showed a 69.8% success rate in Graf III and Graf IV hips while the success rate was significantly lower in the Pavlik group, 53.9% (p = 0.033). For infants older than three months of age, the Tübingen group showed a 71.4% success rate, and the Pavlik group a 54.4% success rate (p = 0.047).

Conclusion: The Tübingen splint should be the preferred treatment option for children older than three months, and for those with severe forms of DDH such as Graf grade III and IV, who are younger than six months at time of diagnosis. The Tübingen hip flexion splint is a valid alternative to the Pavlik harness for older infants and those with more severe DDH. Cite this article:  2021;103-B(5):991-998.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1302/0301-620X.103B5.BJJ-2020-1946.R1DOI Listing
May 2021

Corrigendum to "The interplay of signaling pathway in endothelial cells-Matrix stiffness dependency with targeted-therapeutic drugs" [BBA-Mol. Basis Dis. 1866 (2020) 165645].

Biochim Biophys Acta Mol Basis Dis 2021 Apr 28:166140. Epub 2021 Apr 28.

Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400030, China. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbadis.2021.166140DOI Listing
April 2021

Updated analysis of pediatric clinical studies registered in ClinicalTrials.gov, 2008-2019.

BMC Pediatr 2021 Apr 30;21(1):212. Epub 2021 Apr 30.

Department of Epidemiology and Health Statistics, West China School of Public Health and West China fourth Hospital, Sichuan University, Chengdu, Sichuan Province, China.

Background: Since the national clinical trials registry ( ClinicalTrials.gov ) launched in February 2000, more than 360,000 research studies in the United States and over 200 countries have registered. As the characteristics of pediatric clinical studies keep changing over time and the results-reporting mechanism is under evolving, to know about the relevant updates of data elements and the effect of policies on the quality of reporting results is significant.

Methods: In this research, 53,060 clinical studies related to children registered from January 2008 to December 2019 were downloaded from ClinicalTrials.gov on August 1st, 2020. Different types of studies and critical categorical variables were identified, based on which, Cochran-Armitage test was performed to explore temporal trend of study characteristics and common pediatric clinical conditions in four time subsets. Further, to examine heterogeneity among subgroups (funding sources, funding sites, pediatric clinical conditions,etc), chi-squared test was applied.

Results: A total of 36,136 clinical trials and 16,692 observational studies were identified during the study period. The pediatric clinical trials increased from 7,029 (January 2008-December 2010) to 11,738 (January 2017-December 2019). The number of missing data has declined, with the maximum extent decline from 3.7 to 0.0% (Z = - 15.90, p <  0.001). Drug trials decreased from 48.8 to 28.9% (Z = - 24.68, p <  0.001). Behavioral trials, on the other hand, increased from 12.6 to 20.4% (Z = 12.28, p <  0.001). Most pediatric clinical trials were small-scale (58.9% enrolling 1-100 participants), single-site (61.4%) and funded neither by industry nor by the NIH (59.2%). The proportion of reporting study results varied by study type (χ = 1,256.8, p <  0.001), lead sponsor (χ = 4,545.6, p <  0.001), enrollment (χ = 29.4, p <  0.001) and trial phase (χ = 218.8, p <  0.001).

Conclusion: Pediatric clinical studies registered in ClinicalTrials.gov were dominated by small-scale interventional trials, containing significant heterogeneity in funding sources, funding sites, pediatric clinical conditions and study characteristics. Although the results database has evolved in the past decade, efforts to strengthen the practice of systematic reporting must be continued.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12887-021-02658-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086350PMC
April 2021

Characterizing the Role of Orco Gene in Detecting Aggregation Pheromone and Food Resources in Leiws (Coleoptera: Scarabaeidae).

Front Physiol 2021 13;12:649590. Epub 2021 Apr 13.

Institute of Plant Protection, Hebei Academy of Agriculture and Forestry Sciences, Integrated Pest Management Center of Hebei Province, Baoding, China.

An accurate olfactory system for recognizing semiochemicals and environmental chemical signals plays crucial roles in survival and reproduction of insects. Among all olfaction-related proteins, olfactory receptors (ORs) contribute to the conversion of chemical stimuli to electric signals and thereby are vital in odorant recognition. Olfactory receptor co-receptor (Orco), one of the most conserved ORs, is extremely essential in recognizing odorants through forming a ligand-gated ion channel complex with conventional ligand-binding odorant receptors. We have previously identified aggregation pheromone in (Coleoptera: Scarabaeidae), a native agricultural and horticultural pest in East-Asia. However, to our best knowledge, its olfaction recognition mechanisms are still veiled. To illustrate how recognize aggregation pheromone and host plants, in the present study we cloned and sequenced the full-length gene from antennae (named ) and found that is highly conserved and similar to Orcos from other Coleoptera insects. Our real-time quantitative PCR (qRT-PCR) results showed that is mainly expressed in antenna. We also demonstrated that silencing using RNA interference through injecting dsOrco fragment significantly inhibited expression in comparison with injecting control dsGFP and subsequently revealed using electroantennogram and behavioral bioassays that decreasing transcript abundance significantly impaired the responses of to intraspecific aggregation pheromone and prolonged the time of spending on food seeking. Overall, our results demonstrated that is crucial in mediating odorant perception in .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2021.649590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076894PMC
April 2021

Total Synthesis and Structural Reassignment of Laingolide A.

Mar Drugs 2021 Apr 27;19(5). Epub 2021 Apr 27.

State Key Laboratory of Chemical Oncogenomics, Peking University Shenzhen Graduate School, Shenzhen 518055, China.

The asymmetric total synthesis of four diastereomers of laingolide A was achieved, which led to the unambiguous assignment of the stereochemistry of the natural product. The salient features of the convergent, fully stereocontrolled approach were a copper-catalysed stereospecific Kumada-type coupling, a Julia-Kocienski olefination and an RCM/alkene migration sequence to access the desired macrocyclic enamide.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/md19050247DOI Listing
April 2021

Improved Performance of D-Psicose 3-Epimerase by Immobilisation on Amino-Epoxide Support with Intense Multipoint Attachment.

Foods 2021 Apr 11;10(4). Epub 2021 Apr 11.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China.

D-allulose is an epimer of D-fructose at the C-3 position. With similar sweetness to sucrose and a low-calorie profile, D-allulose has been considered a promising functional sweetener. D-psicose 3-epimerase (DPEase; EC 5.1.3.30) catalyses the synthesis of D-allulose from D-fructose. Immobilised enzymes are becoming increasingly popular because of their better stability and reusability. However, immobilised DPEase generally exhibits less activity or poses difficulty in separation. This study aimed to obtain immobilised DPEase with high catalytic activity, stability, and ease of separation from the reaction solution. In this study, DPEase was immobilised on an amino-epoxide support, ReliZyme HFA403/M (HFA), in four steps (ion exchange, covalent binding, glutaraldehyde crosslinking, and blocking). Glycine-blocked (four-step immobilisation) and unblocked (three-step immobilisation) immobilised DPEase exhibited activities of 103.5 and 138.8 U/g support, respectively, but contained equal amounts of protein. After incubation at 60 °C for 2 h, the residual activity of free enzyme decreased to 12.5%, but the activities of unblocked and blocked DPEase remained at 40.9% and 52.3%, respectively. Immobilisation also altered the substrate specificity of the enzyme, catalysing L-sorbose to L-tagatose and D-tagatose to D-sorbose. Overall, the immobilised DPEase with intense multipoint attachment, especially glycine-blocked DPEase, showed better properties than the free form, providing a superior potential for D-allulose biosynthesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/foods10040831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069956PMC
April 2021

Screening and Selection of a New Medium for Diosgenin Production via Microbial Biocatalysis of sp.

Pharmaceuticals (Basel) 2021 Apr 21;14(5). Epub 2021 Apr 21.

Division for Medicinal Microorganisms Related Strains, CAMS Collection Center of Pathogenic Microorganisms, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.

Steroidal saponins are widely used as starting precursors and medical intermediates for the semi-/total-synthesis of hundreds of steroidal drugs. One such steroidal saponin is diosgenin, which has attracted significant attention due to the huge market demand in the pharmaceutical industry. Due to water waste and severe environmental pollution, the traditional diosgenin production process based on direct acid hydrolysis is no longer used. In this study, to develop a submerged fermentation (SmF) medium for clean diosgenin production via efficient microbial biocatalysis, the Box-Behnken design (BBD) in combination with the Plackett-Burman design (PBD) was used to determine the medium compositions for strains. Three components (wheat bran, phosphate, and Tween-80) were determined as significant factors by the PBD. Using the BBD, the three significant factors were further optimized, and the optimum values were determined for maximal diosgenin production. With 21.16 g/L of wheat bran, 9.60 g/L of phosphate, and 1.97 g/L of Tween-80, the diosgenin yield was 2.28%, i.e., 3.17 mg/L/h. The experimental values agreed with the predicted values, representing a significant increase in diosgenin production compared to its production using the basic SmF medium. For the first time, we reported the development of a new medium for strains to produce diosgenin via microbial biocatalysis of the root of C. H. Wright (DZW). A simple-composition, low-cost, and high-efficiency medium was developed for the first time for the SmF of strains. The medium is considered useful for large-scale SmF and may be applicable to other fungi. This study lays a solid foundation for diosgenin production in an acid-free and wastewater-free way. It may also provide fundamental support for producing other value-added products via microbial biocatalysis of low-value materials by endophytic fungi.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ph14050390DOI Listing
April 2021

Metformin Inhibits the Urea Cycle and Reduces Putrescine Generation in Colorectal Cancer Cell Lines.

Molecules 2021 Apr 1;26(7). Epub 2021 Apr 1.

Department of Anatomy, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, China.

The urea cycle (UC) removes the excess nitrogen and ammonia generated by nitrogen-containing compound composites or protein breakdown in the human body. Research has shown that changes in UC enzymes are not only related to tumorigenesis and tumor development but also associated with poor survival in hepatocellular, breast, and colorectal cancers (CRC), etc. Cytoplasmic ornithine, the intermediate product of the urea cycle, is a specific substrate for ornithine decarboxylase (ODC, also known as ODC1) for the production of putrescine and is required for tumor growth. Polyamines (spermidine, spermine, and their precursor putrescine) play central roles in more than half of the steps of colorectal tumorigenesis. Given the close connection between polyamines and cancer, the regulation of polyamine metabolic pathways has attracted attention regarding the mechanisms of action of chemical drugs used to prevent CRC, as the drug most widely used for treating type 2 diabetes (T2D), metformin (Met) exhibits antitumor activity against a variety of cancer cells, with a vaguely defined mechanism. In addition, the influence of metformin on the UC and putrescine generation in colorectal cancer has remained unclear. In our study, we investigated the effect of metformin on the UC and putrescine generation of CRC in vivo and in vitro and elucidated the underlying mechanisms. In nude mice bearing HCT116 tumor xenografts, the administration of metformin inhibited tumor growth without affecting body weight. In addition, metformin treatment increased the expression of monophosphate (AMP)-activated protein kinase (AMPK) and p53 in both HCT116 xenografts and colorectal cancer cell lines and decreased the expression of the urea cycle enzymes, including carbamoyl phosphate synthase 1 (CPS1), arginase 1 (ARG1), ornithine trans-carbamylase (OTC), and ODC. The putrescine levels in both HCT116 xenografts and HCT116 cells decreased after metformin treatment. These results demonstrate that metformin inhibited CRC cell proliferation via activating AMPK/p53 and that there was an association between metformin, urea cycle inhibition and a reduction in putrescine generation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules26071990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038129PMC
April 2021