Publications by authors named "Ning Ji"

129 Publications

EA-Directing Formamidinium-Based Perovskite Microwires with A-Site Doping.

ACS Omega 2021 Mar 8;6(10):7157-7164. Epub 2021 Mar 8.

School of Science and Engineering and Shenzhen Key Lab of Semiconductor Lasers, The Chinese University of Hong Kong, Shenzhen, Guangdong 518172, China.

One recent development to improve optoelectronic properties of perovskites is to use a larger cation for multication engineering. The chain-like ethylammonium (EA) [(CH)NH] cation is more likely to form a one-dimensional perovskite structure; however, there is no remarkable evidence in this connection. Therefore, in this work, for the first time, the EA cation as an alternative cation was introduced into FAPbBr cubic crystals to explore the stabilities and optoelectronic properties of mixed FA EAPbBr perovskites. The results indicate that replacing FA with EA is a more effective way to realize band gap tuning and morphology transformation between the cubic shape and microwires. The tuned band gap of perovskite is due to the variation of Pb-Br-Pb angles induced by the insertion of the larger EA cation. We highlight that this work provides new physical insights into the correlation between the engineering of organic cations and the formation of perovskite microwires and the tunable band gap. This observation will help us to find new ways to grow perovskite microwires and subsequently study the optoelectronic performance of low-dimensional perovskites devices.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsomega.1c00213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970562PMC
March 2021

Hyperglycemia accelerates inflammaging in the gingival epithelium through inflammasomes activation.

J Periodontal Res 2021 Mar 2. Epub 2021 Mar 2.

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

Background And Objective: Diabetes accelerates inflammaging in various tissue with an increase in senescent cell burden and senescence-associated secretory phenotype (SASP) secretion, which is a significant cause of tissue dysfunction and contributes to the diabetic complications. Recently, inflammasomes are thought to contribute to inflammaging. Here, utilizing diabetic models in vivo and in vitro, we investigated the potential association between hyperglycemia-induced inflammaging and gingival tissue dysfunction and the mechanism underlying inflammasome-associated inflammaging.

Materials And Methods: Gingival epithelium and serum were collected from control and diabetic patients and mice. The expression of p16, p21, and inflammasomes in the gingival epithelium, SASP factors in serum, and the molecular factors associated with gingival epithelial barrier function were assessed. Human oral keratinocyte (HOK) was stimulated with normal and high glucose, and pre-treated with Z-YVAD-FMK (Caspase-1 inhibitor) prior to evaluating cellular senescence, SASP secretion, and inflammasome activation.

Results: In vivo, hyperglycemia significantly elevated the local burden of senescent cells in the gingival epithelium and SASP factors in the serum and simultaneously reduced the expression levels of Claudin-1, E-cadherin, and Connexin 43 in the gingival epithelium. Interestingly, the inflammasomes were activated in the gingival epithelium. In vitro, high glucose-induced the inflammaging in HOK, and blocking inflammasome activation through inhibiting Caspase-1 and glucose-induced inflammaging.

Conclusions: Hyperglycemia accelerated inflammaging in the gingival epithelium through inflammasomes activation, which is potentially affiliated with a decline in the gingival epithelial barrier function in diabetes. Inflammasomes-related inflammaging may be the crucial mechanism underlying diabetic periodontitis and represents significant opportunities for advancing prevention and treatment options.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jre.12863DOI Listing
March 2021

The Dual Role of Macropinocytosis in Cancers: Promoting Growth and Inducing Methuosis to Participate in Anticancer Therapies as Targets.

Front Oncol 2020 19;10:570108. Epub 2021 Jan 19.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Macropinocytosis is an important mechanism of internalizing extracellular materials and dissolved molecules in eukaryotic cells. Macropinocytosis has a dual effect on cancer cells. On the one hand, cells expressing RAS genes (such as K-RAS, H-RAS) under the stress of nutrient deficiency can spontaneously produce constitutive macropinocytosis to promote the growth of cancer cells by internalization of extracellular nutrients (like proteins), receptors, and extracellular vesicles(EVs). On the other hand, abnormal expression of RAS genes and drug treatment (such as MOMIPP) can induce a novel cell death associated with hyperactivated macropinocytosis: methuosis. Based on the dual effect, there is immense potential for designing anticancer therapies that target macropinocytosis in cancer cells. In view of the fact that there has been little review of the dual effect of macropinocytosis in cancer cells, herein, we systematically review the general process of macropinocytosis, its specific manifestation in cancer cells, and its application in cancer treatment, including anticancer drug delivery and destruction of macropinocytosis. This review aims to serve as a reference for studying macropinocytosis in cancers and designing macropinocytosis-targeting anticancer drugs in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.570108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851083PMC
January 2021

Reversal of Cancer Multidrug Resistance (MDR) Mediated by ATP-Binding Cassette Transporter G2 (ABCG2) by AZ-628, a RAF Kinase Inhibitor.

Front Cell Dev Biol 2020 8;8:601400. Epub 2020 Dec 8.

Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, United States.

Overexpression of ABCG2 remains a major impediment to successful cancer treatment, because ABCG2 functions as an efflux pump of chemotherapeutic agents and causes clinical multidrug resistance (MDR). Therefore, it is important to uncover effective modulators to circumvent ABCG2-mediated MDR in cancers. In this study, we reported that AZ-628, a RAF kinase inhibitor, effectively antagonizes ABCG2-mediated MDR . Our results showed that AZ-628 completely reversed ABCG2-mediated MDR at a non-toxic concentration (3 μM) without affecting ABCB1-, ABCC1-, or ABCC10 mediated MDR. Further studies revealed that the reversal mechanism was by attenuating ABCG2-mediated efflux and increasing intracellular accumulation of ABCG2 substrate drugs. Moreover, AZ-628 stimulated ABCG2-associated ATPase activity in a concentration-dependent manner. Docking and molecular dynamics simulation analysis showed that AZ-628 binds to the same site as ABCG2 substrate drugs with higher score. Taken together, our studies indicate that AZ-628 could be used in combination chemotherapy against ABCG2-mediated MDR in cancers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2020.601400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753047PMC
December 2020

Blood Pressure Modulation With Low-Intensity Focused Ultrasound Stimulation to the Vagus Nerve: A Pilot Animal Study.

Front Neurosci 2020 12;14:586424. Epub 2020 Nov 12.

CAS Key Laboratory of Human-Machine Intelligence-Synergy Systems and Research Center for Neural Engineering, Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), and the SIAT Branch, Shenzhen Institute of Artificial Intelligence and Robotics for Society, Shenzhen, China.

Objective: For hypertensive individuals, their blood pressure (BP) is often managed by taking medications. However, antihypertensive drugs might cause adverse effects such as congestive heart failure and are ineffective in significant numbers of the hypertensive population. As an alternative method for hypertension management, non-drug devices-based neuromodulation approaches such as functional electrical stimulation (FES) have been proposed. The FES approach requires the implantation of a stimulator into the body. One recently emerging technique, called low-intensity focused ultrasound stimulation (FUS), has been proposed to non-invasively modulate neural activities. In this pilot study, the feasibility of adopting low-intensity FUS neuromodulation for BP regulation was investigated using animal models.

Methods: A FUS system was developed for BP modulation in rabbits. For each rabbit, the low-intensity FUS with different acoustic intensities was used to stimulate its exposed left vagus nerve, and the BP waveform was synchronously recorded in its right common carotid artery. The effects of the different FUS intensities on systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MAP), and heart rate (HR) were extensively examined from the BP recordings.

Results: The results demonstrated that the proposed FUS method could successfully induce changes in SBP, DBP, MAP, and HR values. When increasing acoustic intensities, the values of SBP, DBP, and MAP would tend to decrease more substantially.

Conclusion: The findings of this study suggested that BP could be modulated through the FUS, which might provide a new way for non-invasive and non-drug management of hypertension.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnins.2020.586424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693571PMC
November 2020

Preparation of genetically engineered murine SINE RNA without endotoxin contamination.

MethodsX 2020 16;7:101102. Epub 2020 Oct 16.

Department of Genetics, Hebei Key Lab of Laboratory Animal, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang 050017, Hebei Province, China.

RNAs have been elucidated to play the critical role in regulating gene expression and to be expected as effective drugs in the treatment of cancer and age-related diseases. RNAs are extracted by SDS-NaCl centrifugation after transformation of by expression vectors, which is a method to obtain genetically engineered RNAs. But the prepared RNAs by this method contain endotoxin, which limits their application and in cell experments. Here we improved SDS-NaCl filtration method based on SDS-NaCl centrifugation method. Endotoxin removal efficiency of SDS-NaCl filtration was nearly 4.2 times more than did SDS-NaCl centrifugation. Triton X-114 phase separation was used to reduce futher the endotoxin content of SDS-NaCI filtration-extracted RNA (from 11.25 EU/µg RNA/ml to 0.08 EU/µg RNA/ml). RNA prepared using the methods established in this paper meets the requirements for and cell culture experiments. Here we describe the process of preparing endotoxin-free B1as RNA from pET-B1as-DE3 (DE3 transformed by pET-B1as expression vector which containing a tandem SINE B1 elements) using SDS-NaCl filtration incorporating Triton X-114 phase separation.•The endotoxin removal efficiency of SDS-NaCl filtration is higher than that of SDS-NaCl centrifugation.•RNA prepared by SDS-NaCl filtration incorporating Triton X-114 meets the requirements for experiments on animals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mex.2020.101102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644746PMC
October 2020

Repurposing disulfiram to induce OSCC cell death by cristae dysfunction promoted autophagy.

Oral Dis 2020 Sep 28. Epub 2020 Sep 28.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Medicine of Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Objective: Disulfiram has been repurposed as a potential candidate to suppress various cancers. However, its anti-tumor effects and molecular mechanisms of oral squamous cell carcinoma remain unclear. In this study, we aimed to assess the anti-cancer activity and underlying mechanisms of disulfiram in the context of oral squamous cell carcinoma.

Materials And Methods: We tested the cytotoxicity of disulfiram in oral squamous cell carcinoma using a 3D culture model and a PDX model. Cell proliferation, cell death, and related signaling pathways were evaluated. Mitochondrial DNA copy number, mitochondrial respiration, mitochondrial mass, and mitochondrial complexes were analyzed.

Results: Disulfiram can induce excessive autophagy in oral squamous cell carcinoma cells as a result of OXPHOS deficiency. Disulfiram-induced OPA1 degradation can impair the functional cristae structure, which results in a dramatic reduction in mitochondrial respiration capability as well as ATP production. Subsequently, energy deprivation leads to excessive autophagy through AMPK activation. In addition, exogenous ATP blocked the activation of AMPK and rescued disulfiram-induced cell death.

Conclusion: DSF targets mitochondrial inner membrane protein OPA1 to disturb the energy supply, triggering excessive autophagy, and cell death in OSCC. Our study suggests OPA1-dependent ATP generation is pharmacologically targetable in OSCC treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/odi.13652DOI Listing
September 2020

A new Zn metallocryptand with unprecedented diflexure helix induced by V-shaped diimidazole building blocks.

Acta Crystallogr B Struct Sci Cryst Eng Mater 2020 Jun 16;76(Pt 3):411-416. Epub 2020 May 16.

School of Chemical Engineering, Guizhou Minzu University, Guiyang, Guizhou 550025, People's Republic of China.

Taking advantage of V-shaped ligands, a Zn metallocryptand, namely {[Zn(didp)(m-bdc)]}, (1) [didp = 2,8-di(1H-imidazol-1-yl)-dibenzothiophene and m-Hbdc = isophthalic acid], has been hydrothermally synthesized. Single-crystal X-ray diffraction analysis reveals a 26-membered butterfly-type metallomacrocycle [Zn(didp)]. One m-bdc ligand bridges [Zn(didp)] units to form a laterally non-symmetric [Zn(didp)(m-bdc)] metallocryptand with an exo-exo conformation. Another crystallographically independent m-bdc functions as a secondary synthon to bridge discrete metallocryptands into a 1D zigzag chain architecture. Undoubtedly, the choice of two matched ligands in this work is crucial for metallocryptand construction and structure expansion. Interestingly, a rare helical chain with two flexures in one single L and/or R strand is observed. Another important feature is the C-O...π interactions, by which the dimensionality extension of (1) can be induced. Fluorescence measurements and density functional theory (DFT) calculations illustrate that the emission of (1) can probably be attributed to ligand-to-ligand charge transfer (LLCT).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1107/S2052520620004217DOI Listing
June 2020

miR-223 regulates oral squamous cell carcinoma metastasis through the Wnt/β-catenin signaling pathway.

Oral Oncol 2020 Aug 18;109:104941. Epub 2020 Aug 18.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China. Electronic address:

Objectives: Metastasis seriously affects the prognosis of patients with oral squamous cell carcinoma (OSCC); however, the precise mechanism remains poorly understood.

Materials And Methods: microRNA (miRNA) array analysis of four cell lines was used to identify candidate miRNAs. The Cancer Genome Atlas (TCGA) database was used to verify the relationship between candidate miRNAs and OSCC metastasis. Transwell chambers and mouse model experiments were used to analyze OSCC cell migration and invasion abilities in vitro and in vivo. Additionally, bioinformatics and a dual luciferase reporter assay were used to identify selected miRNA target genes. A multicenter clinical cohort of 250 patients with OSCC was set up to evaluate the diagnostic and predicted value of the target genes. Finally, the molecular mechanism of a selected miRNA regulating OSCC metastasis was further explored.

Results: miR-223 expression was found to be negatively correlated with OSCC cell invasion and migration abilities. TCGA database data confirmed the relationship between miR-223 expression and OSCC metastasis. Functional experiments indicated that overexpression of miR-223 could decrease the metastasis ability of OSCC cells, while decreasing its expression level led to the enhancement of OSCC metastasis. Bioinformatics and a dual-luciferase reporter assay identified that miR-223 directly targets transcription factor 7-like 2 (TCF7L2). Additionally, TCF7L2 was shown to be negatively correlated with patient metastasis and survival.

Conclusions: miR-223 regulates OSCC invasion and metastasis by directly targeting TCF7L2 and potentiating the Wnt/β-catenin signaling pathway. These findings demonstrate the versatile role of miR-223 in carcinogenesis. miR-223 might serve as an attractive OSCC metastasis intervention target.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.oraloncology.2020.104941DOI Listing
August 2020

Critical Residues and Contacts within Domain IV of Autographa californica Multiple Nucleopolyhedrovirus GP64 Contribute to Its Refolding during Membrane Fusion.

J Virol 2020 09 15;94(19). Epub 2020 Sep 15.

State Key Laboratory of Crop Stress Biology for Arid Areas, Key Laboratory of Northwest Loess Plateau Crop Pest Management of Ministry of Agriculture, College of Plant Protection, Northwest A&F University, Yangling, China

Autographa californica multiple nucleopolyhedrovirus (AcMNPV) GP64 is a class III viral fusion protein that mediates low-pH-triggered membrane fusion during virus entry. Although the structure of GP64 in a postfusion conformation has been solved, its prefusion structure and the mechanism of how the protein refolds to execute fusion are unknown. In its postfusion structure, GP64 is composed of five domains (domains I to V). Domain IV (amino acids [aa] 374 to 407) contains two loops (loop 1 and loop 2) that form a hydrophobic pocket at the membrane-distal end of the molecule. To determine the roles of domain IV, we used alanine-scanning mutagenesis to replace each of the individual residues and the contact-forming residues within domain IV and evaluate their contributions to GP64-mediated membrane fusion and virus infection. In many cases, replacement of a single amino acid had no significant impact on GP64. However, replacement of R392 or disruption of the N381-N385, N384-Y388, N385-W393, or K389-W393 contact resulted in poor cell surface expression and fusion loss of the modified GP64, whereas replacement of E390 or G391 or disruption of the N381-K389, N381-Q401, or N381-I403 contact reduced the cell surface expression level of the constructs and the ability of GP64 to mediate fusion pore expansion. In contrast, replacement of N407 or disruption of contact D404-S406 appeared to restrict fusion pore expansion without affecting expression. Combined with the finding that these constructs remain in the prefusion conformation or have a dramatically less efficient transition from the prefusion to the postfusion state under acidic conditions, we proposed that domain IV is necessary for refolding of GP64 during membrane fusion. Baculovirus GP64 is grouped with rhabdovirus G, herpesvirus gB, and thogotovirus glycoproteins as a class III viral fusion protein. In their postfusion structures, these proteins contain five domains (domains I to V). Distinct from domain IV of rhabdovirus G and herpesvirus gB proteins, which is composed of β-sheets, domain IV of GP64 is a loop region; the same domain in thogotovirus glycoproteins has not been solved. In addition, domain IV is proximal to domain I (fusion domain) in prefusion structures of vesicular stomatitis virus (VSV) G and human cytomegalovirus (HCMV) gB but resides at the domain I-distal end of the molecule in a postfusion conformation. In this study, we identified that highly conserved residues and contacts within domain IV of AcMNPV GP64 are necessary for low-pH-triggered conformational change and fusion pore expansion. Our results highlight the roles of domain IV of class III viral fusion proteins in refolding during membrane fusion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/JVI.01105-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495389PMC
September 2020

Isorhamnetin induces the paraptotic cell death through ROS and the ERK/MAPK pathway in OSCC cells.

Oral Dis 2021 Mar 30;27(2):240-250. Epub 2020 Jul 30.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, Sichuan University, Chengdu, China.

Objective: There were rarely investigations on the effects and molecular mechanisms of oral squamous cell carcinoma (OSCC) cells when treated with isorhamnetin. This article assesses the anti-cancer effect of isorhamnetin.

Methods And Materials: Oral squamous cell carcinoma cells were treated with or without isorhamnetin. Cell proliferation, cell cycle arrest, cell migration, cell death, and the related signaling pathways were evaluated.

Results: The results revealed that cell proliferation was inhibited in a dose- and time-dependent manner, which was confirmed by diminished cell viability and revealed by decreased in the number of cell colonies. In addition, the cell cycle arrested in the G2/M phase, and the protein levels of cyclin B1 and CDC2 were suppressed. Moreover, the cell migration was inhibited, and the protein levels of related proteins were modulated. Furthermore, it could be observed that abundant cytoplasmic vacuoles existed which that were derived from mitochondria and the endoplasmic reticulum. It was confirmed that cell death did not result from apoptosis and may have which may be apt to paraptosis. Isorhamnetin was observed to upregulate phosphorylated ERK cascades and increase intracellular reactive oxygen species levels.

Conclusions: Our study suggested that the anti-cancer effect of isorhamnetin might trigger paraptosis, which may indicate a new therapeutic approach to OSCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/odi.13548DOI Listing
March 2021

Modulating the function of ABCB1: in vitro and in vivo characterization of sitravatinib, a tyrosine kinase inhibitor.

Cancer Commun (Lond) 2020 07 11;40(7):285-300. Epub 2020 Jun 11.

Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, New York, 11439, USA.

Background: Overexpression of ATP-binding cassette (ABC) transporter is a major contributor to multidrug resistance (MDR), in which cancer cells acquire resistance to a wide spectrum of chemotherapeutic drugs. In this work, we evaluated the sensitizing effect of sitravatinib, a broad-spectrum tyrosine kinase inhibitor (TKI), on ATP-binding cassette subfamily B member 1 (ABCB1)- and ATP-binding cassette subfamily C member 10 (ABCC10)-mediated MDR.

Methods: MTT assay was conducted to examine cytotoxicity and evaluate the sensitizing effect of sitravatinib at non-toxic concentrations. Tritium-labeled paclitaxel transportation, Western blotting, immunofluorescence analysis, and ATPase assay were carried out to elucidate the mechanism of sitravatinib-induced chemosensitization. The in vitro findings were translated into preclinical evaluation with the establishment of xenograft models.

Results: Sitravatinib considerably reversed MDR mediated by ABCB1 and partially antagonized ABCC10-mediated MDR. Our in silico docking simulation analysis indicated that sitravatinib strongly and stably bound to the transmembrane domain of ABCB1 human-mouse chimeric model. Furthermore, sitravatinib inhibited hydrolysis of ATP and synchronously decreased the efflux function of ABCB1. Thus, sitravatinib could considerably enhance the intracellular concentration of anticancer drugs. Interestingly, no significant alterations of both expression level and localization of ABCB1 were observed. More importantly, sitravatinib could remarkably restore the antitumor activity of vincristine in ABCB1-mediated xenograft model without observable toxic effect.

Conclusions: The findings in this study suggest that the combination of sitrvatinib and substrate antineoplastic drugs of ABCB1 could attenuate the MDR mediated by the overexpression of ABCB1.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cac2.12040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365458PMC
July 2020

Chinese massage, Tui Na, combined with herbs improves clinical symptoms and regulates sex hormones in patients with mammary gland hyperplasia.

Medicine (Baltimore) 2020 May;99(21):e20300

Department of Massage, Traditional Chinese Medicine Hospital of Xinjiang Uyghur Autonomous Region, Urumqi, Xinjiang, China.

To study the effects of Tui Na therapy on patients with mammary gland hyperplasia.A total of 68 female patients with mammary gland hyperplasia were included in this retrospective study from May 2016 to May 2017 and assigned into control group (N = 34) treated with Rupixiao only (a proprietary Chinese medicine) or Tui Na group (N = 34) treated with Tui Na (Chinese massage) combined with Rupixiao. The pain intensity (visual analogous scale, VAS) and serum levels of luteinizing hormone (LH), estradiol (E2), prolactin (PRL), and progesterone (P) were examined before and after the treatment.The efficacies were 94.1% (32/34) in the Tui Na group and 76.5% (26/34) in the control group (P = .04). After treatment, VAS in Tui Na groups was significantly lower than that in control group (2.1 ± 1.1 vs 3.1 ± 1.1, P < .05). After follow-up for five months, the recurrence rates were 12.5% (4/32) in the Tui Na group and 23.1% (6/26) in the control group (P = .01). The levels of all 4 hormones in the Tui Na group increased significantly after treatment. In control group, only LH and E2 levels were significantly increased after treatment.In patients with mammary gland hyperplasia, Tui Na combined with Rupixiao could improve clinical symptoms, regulate sex hormone levels, and decrease the recurrence rate than Rupixiao alone. Our finding suggests that Tui Na can be potentially used for the treatment of mammary gland hyperplasia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000020300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249953PMC
May 2020

Metformin ameliorates the NLPP3 inflammasome mediated pyroptosis by inhibiting the expression of NEK7 in diabetic periodontitis.

Arch Oral Biol 2020 Aug 16;116:104763. Epub 2020 May 16.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, 3rd Section S Renmin Road, 14#, Chengdu, PR China; Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, PR China. Electronic address:

Objectives: To investigate the underlying mechanism between diabetic periodontitis and NLR family pyrin domain containing 3 (NLRP3) inflammasome associated pyroptosis.

Design: Experimental models of diabetes-associated periodontitis were implemented in db/db mice. We detected NLRP3 inflammasome related cytokines and gasdermin D (GSDMD) both in vitro and in vivo. We performed bioinformatics predictions based on microarray analysis using bone marrow derived macrophages (BMDMs).

Results: Diabetes-associated periodontitis mice exhibited the worst fasting glucose and alveolar bone destruction. GSDMD positive cells and NLRP3 inflammasome expression were augmented in gingival tissue, which were partly reversed by metformin. In vitro data suggested NLRP3 inflammasomes stimuli induced cell pyroptotic death and deletion of NLRP3 decreased GSDMD expression. We found a profile of differential lncRNAs expression and three co-expressed lncRNAs of nlrp3 and gsdmd in BMDMs.

Conclusions: Our data show that NLRP3 mediated pyroptosis has a significant role in diabetes-associated periodontitis. The pyroptotic cell death may be the pivot reason of the deteriorated inflammation in this disease, which is ameliorated by metformin treatment. Moreover, the role of both NLRP3 and GSDMD may be regulated by lncRNA_1810058I24Rik, lncRNA_Gm12474 and lncRNA_Gm41514.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.archoralbio.2020.104763DOI Listing
August 2020

Sitravatinib, a Tyrosine Kinase Inhibitor, Inhibits the Transport Function of ABCG2 and Restores Sensitivity to Chemotherapy-Resistant Cancer Cells .

Front Oncol 2020 12;10:700. Epub 2020 May 12.

Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, United States.

Sitravatinib, also called MGCD516 or MG-516, is a broad-spectrum tyrosine kinase inhibitor (TKI) under phase III clinical evaluation. Herein, we explored the activity of sitravatinib toward multidrug resistance (MDR) by emphasizing its inhibitory effect on ATP-binding cassette super-family G member 2 (ABCG2). ABCG2 is a member of ATP-binding cassette (ABC) transporter family and plays a critical role in mediating MDR. Sitravatinb received an outstanding docking score for binding to the human ABCG2 model (PDB code: 6ETI) among thirty screened TKIs. Also, an MTT assay indicated that sitravatinib at 3 μM had the ability to restore the antineoplastic effect of various ABCG2 substrates in both drug-selected and gene-transfected ABCG2-overexpressing cell lines. In further tritium-labeled mitoxantrone transportation study, sitravatinib at 3 μM blocked the efflux function mediated by ABCG2 and as a result, increased the intracellular concentration of anticancer drugs. Interestingly, sitravatinib at 3 μM altered neither protein expression nor subcellular localization of ABCG2. An ATPase assay demonstrated that ATPase activity of ABCG2 was inhibited in a concentration-dependent manner with sitravatinib; thus, the energy source to pump out compounds was interfered. Collectively, the results of this study open new avenues for sitravatinib working as an ABCG2 inhibitor which restores the antineoplastic activity of anticancer drugs known to be ABCG2 substrates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.00700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236772PMC
May 2020

The preparation of endotoxin-free genetically engineered murine B1 antisense RNA.

Anal Biochem 2020 06 17;599:113737. Epub 2020 Apr 17.

Department of Genetics, Hebei Medical University, Hebei Key Lab of Laboratory Animal, Shijiazhuang, 050017, Hebei Province, China. Electronic address:

One of the major limitations in the production of genetically engineered RNA from Escherichia coli (E. coli) is contamination by endotoxin. Here we report the first method that is capable of removing endotoxin from genetically engineered RNA. As a proof of concept, we transformed E. coli with a plasmid containing a tandem short interspersed nuclear elements from the mouse genome (SINE B1 elements). We then evaluated several extraction methods (SDS-NaCl centrifugation, SDS-NaCl filtration, TRIzol and SDS hot-phenol) and refinements thereof, and measured the resulting RNA yield, RNA purity, RNA integrity and endotoxin content. SDS-NaCl filtration with 2 mol/L NaCl, incorporating DEPC as an RNA protective agent, effectively removed endotoxin and resulted in a good RNA yield. Triton X-114 phase separation further reduced the endotoxin content of SDS-NaCl filtration-extracted RNA. RNA extracted by SDS-NaCl filtration with Triton X-114 phase separation did not cause adverse reactions in BALB/c mice and did not induce fever in rabbits when injected into these animals. The RNA met the requirements of nucleic acid reagents for in vivo experiments on animals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ab.2020.113737DOI Listing
June 2020

Proliferative ability and accumulation of cancer stem cells in oral submucous fibrosis epithelium.

Oral Dis 2020 Apr 8. Epub 2020 Apr 8.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Objectives: The driving force of the malignant transformation of epithelial cells during oral submucous fibrosis (OSF) is an unsettled debate. We hypothesized that the expression and accumulation of cancer stem cells (CSCs) are accompanied by epithelial atrophy in OSF.

Materials And Methods: The expression levels of Ki67 (proliferation marker), SOX2, and Bmi1 (CSC marker) in the epithelium during the early, middle, and late stages of OSF were measured by immunohistochemistry. At the same time, we focused on the expression of three proteins in OSF patients with benign hyperkeratosis and epithelial dysplasia.

Results: The clinical cohort study showed upregulated expression of the proliferation-associated protein Ki67 in atrophic epithelium in patients with OSF. The expression levels of SOX2 and Bmi1 showed an increasing trend in the progression of OSF. Ki67, SOX2, and Bmi1 were highly expressed in OSF tissues with dysplasia. Moreover, the three proteins were located at the epithelial and mesenchymal junctions, and their expression showed a positive correlation with each other.

Conclusion: The results suggest that CSC accumulation could be accompanied by epithelial atrophy during OSF, which may be responsible for the driving forces for OSF carcinogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/odi.13347DOI Listing
April 2020

Influences of different drying methods on the structural characteristics and prebiotic activity of polysaccharides from bamboo shoot (Chimonobambusa quadrangularis) residues.

Int J Biol Macromol 2020 Jul 28;155:674-684. Epub 2020 Mar 28.

Food and Pharmaceutical Engineering Institute, Guiyang University, Guiyang, Guizhou 550005, PR China; Guizhou Engineering Research Center for Fruit Processing, Department of Science and Technology of Guizhou Province, Guiyang, Guizhou 550005, PR China.

In the present study, in order to assess the influences of drying methods on the chemical structures, in vitro digestibility and prebiotic potential of polysaccharides extracted from Chimonobambusa quadrangularis shoot (CPSs), four drying methods, including hot air-, vacuum-, freeze-, and spray-drying, were utilized to dry CPSs. Results revealed that the physicochemical characteristics and prebiotic activity of CPSs varied by different drying methods. In comparison with the other drying methods, freeze-dried CPSs had higher uronic acid content (9.58%), lower medium-high molecular weight (117.63 kDa), smaller particle size (115.97 nm) and better solubility. All four CPSs fractions exhibited low degree of digestibility to pretended human gastric juice (< 2%) and α-amylase (< 5%). The freeze-dried CPSs showed the greatest prebiotic activity as this polysaccharide induced the strongest proliferation effect of probiotic bacteria and the highest production of total short chain fatty acids. Our results collectively provided substantial evidence that the freeze-drying method proposed in this study could be an effective technique in improving the prebiotic potentiality of CPSs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijbiomac.2020.03.223DOI Listing
July 2020

Extraovarian Brenner tumor in the uterus: a case report and review of literature.

Diagn Pathol 2020 Mar 12;15(1):22. Epub 2020 Mar 12.

Department of Pathology, the Fourth Affiliated Hospital of Nanchang University, 133 South Guangchang Road, Nanchang, 330003, China.

Background: Extraovarian Brenner tumors (EOBTs) are extremely rare and can be observed incidentally in both female and male patients, raising concerns regarding the origin of Brenner tumors.

Case Presentation: A 53-year-old postmenopausal woman presented with a nodular lesion in the left side of the corpus uteri, which was found at a routine health check. Macroscopically, the lesion appeared as a solid nodule with a yellowish-gray cut surface, approximately 6 cm in greatest diameter. Microscopically, the lesion consisted of well-defined epithelial nests and spindled stromal cells. Parenchymal cells expressed CK7, GATA3, CK5/6, 34βE12, and p63. A single layer of cavity-lined cells with umbrella-like shape showed apical Uroplakin III positivity. Stromal cells were positive for SMA, ER, and PR. The final diagnosis was EOBT and the patient was followed for 2 months with no recurrence.

Conclusions: We report here the third case of EOBTs in the uterus. The combination of morphologic and immunohistochemical results supported the involvement of urothelial metaplasia in the development of EOBTs. The similarities between EOBTs and Walthard nests made Müllerian epithelium an attractive candidate as the cellular origin. Changes of tissue structure or sex hormones imbalance may lead to the translocation of Müllerian remnants to distant organs, explaining the pathogenesis of EOBTs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13000-019-0906-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066756PMC
March 2020

Interbody Fusion and Percutaneous Reduction For Lumbar Spondylolisthesis With Mobile Microendoscopic Discectomy Technique.

Clin Spine Surg 2020 03;33(2):E63-E70

Department of Minimally Invasive Spine Surgery, Tianjin Hospital, Tianjin, People's Republic of China.

Study Design: A minimally invasive surgical technique for lumbar spondylolisthesis.

Objective: The objective of this study was to investigate the feasibility and clinical efficacy of interbody fusion and percutaneous reduction for lumbar spondylolisthesis using mobile microendoscopic discectomy (MMED) technique.

Summary Of Background Data: Current surgical techniques for lumbar spondylolisthesis cause considerable trauma, so a minimally invasive technique is needed.

Materials And Methods: A total of 62 patients of lumbar spondylolisthesis (40 patients of degenerative spondylolisthesis and 22 patients of isthmic spondylolisthesis) were treated with interbody fusion and percutaneous reduction using the MMED technique. A 2.5-cm longitudinal incision was made on the side of dominant symptoms, with paraspinous approach used for degenerative spondylolisthesis and transforaminal approach for isthmic spondylolisthesis. The fenestration and decompression were performed under MMED. The intervertebral space was released through an outer tube under direct vision, followed by bone graft and cage implantation. Percutaneous pedicle screws were used, with the residual spondylolisthesis further reduced. The patients were followed up to evaluate the clinical results.

Results: The procedure was successful in all patients. Postoperative radiographs showed sufficient decompression and improvement of spinal alignment for both groups. The average reduction rate of the spondylolisthesis was 68% for degenerative spondylolisthesis group and 66% for isthmic spondylolisthesis group. The patients of 2 groups were followed up for 12-24 months. At the final follow-up, the Oswestry Disability Index and Visual Analogue Scale scores decreased significantly compared with preoperation for both groups. The clinical results were excellent in 22 cases, good in 16 and fair in 2 for degenerative spondylolisthesis group, and excellent in 11 cases, good in 10 and fair in 1 for isthmic spondylolisthesis group according to the Macnab Scale.

Conclusion: Interbody fusion and percutaneous reduction with MMED provides a minimally invasive procedure for lumbar spondylolisthesis, with sufficient decompression, reduction, fusion, and satisfactory clinical results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/BSD.0000000000000865DOI Listing
March 2020

Venetoclax, a BCL-2 Inhibitor, Enhances the Efficacy of Chemotherapeutic Agents in Wild-Type ABCG2-Overexpression-Mediated MDR Cancer Cells.

Cancers (Basel) 2020 Feb 18;12(2). Epub 2020 Feb 18.

Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA.

Previous studies have shown that small-molecule BCL-2 inhibitors can have a synergistic interaction with ABCG2 substrates in chemotherapy. Venetoclax is a potent and selective BCL-2 inhibitor, approved by the FDA in 2016 for the treatment of patients with chronic lymphocytic leukemia (CLL). This study showed that, at a non-toxic concentration, venetoclax at 10 µM significantly reversed multidrug resistance (MDR) mediated by wild-type ABCG2, without significantly affecting MDR mediated by mutated ABCG2 (R482G and R482T) and ABCB1, while moderate or no reversal effects were observed at lower concentrations (0.5 to 1 µM). The results showed that venetoclax increased the intracellular accumulation of chemotherapeutic agents, which was the result of directly blocking the wild-type ABCG2 efflux function and inhibiting the ATPase activity of ABCG2. Our study demonstrated that venetoclax potentiates the efficacy of wild-type ABCG2 substrate drugs. These findings may provide useful guidance in combination therapy against wild-type ABCG2-mediated MDR cancer in clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12020466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072352PMC
February 2020

Disrupting the association of Autographa californica multiple nucleopolyhedrovirus Ac93 with cellular ESCRT-III/Vps4 hinders nuclear egress of nucleocapsids and intranuclear microvesicles formation.

Virology 2020 02 12;541:85-100. Epub 2019 Dec 12.

State Key Laboratory of Crop Stress Biology for Arid Areas, Key Laboratory of Integrated Pest Management on Crops in Northwestern Loess Plateau, Ministry of Agriculture, College of Plant Protection, Northwest A&F University, Yangling, Shaanxi, 712100, China. Electronic address:

The endosomal sorting complex required for transport (ESCRT) pathway is required for efficient egress of Autographa californica multiple nucleopolyhedrovirus (AcMNPV). In this study, we found that Ac93, a baculovirus core protein, contains a conserved MIM1-like motif. Alanine substitutions for six leucine residues in MIM1-like motif revealed that L142, L145, L146, and L149 are required for association of Ac93 with the MIT domain of Vps4. Mutations of these residues also blocked self-association and the association of Ac93 with ESCRT-III proteins or other viral core proteins Ac76 and Ac103, and resulted in a substantial reduction of infectious virus production, less efficient nuclear egress of progeny nucleocapsids, and the defect of intranuclear microvesicles formation. Combined with the localization of the association of Ac93 with ESCRT-III/Vps4 and other viral proteins at the nuclear membrane, we propose that the coordinated action of these viral proteins and ESCRT-III/Vps4 may be involved in remodeling the nuclear membrane.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.virol.2019.12.003DOI Listing
February 2020

Nepetin, a natural compound from Inulae flos, suppresses degranulation and eicosanoid generation through PLCγ1 and Akt signaling pathways in mast cells.

Arch Pharm Res 2020 Feb 3;43(2):224-232. Epub 2020 Feb 3.

Department of Korean Medicine Development, National Institute for Korean Medicine Development, Gyeongsan, 38540, Republic of Korea.

Nepetin derived from the flowers of Inula japonica, Inulae flos, has been reported to exert several biological activities, including anti-inflammatory responses. In this study, we evaluated the anti-allergic property of nepetin with its molecular mechanisms in bone marrow-derived mast cells (BMMC) and mice. In this in vitro study, we investigated the inhibitory effects of nepetin on degranulation and generation of leukotriene C (LTC) and prostaglandin D (PGD) in IgE/antigen (Ag)-stimulated BMMC. The effect of nepetin on passive cutaneous anaphylaxis (PCA) reaction was also studied in mice. Nepetin reduced degranulation and LTC generation in BMMC. The IgE/Ag-mediated signaling pathway demonstrated that nepetin suppressed intracellular Ca level and activation of PLCγ1 and cPLA. However, MAPKs were not affected by nepetin in BMMC. In addition, nepetin treatment reduced PGD production and suppressed cyclooxygenase-2 protein expression via the inhibition of the Akt and nuclear factor-κB signaling pathways. With respect to the local allergic response in vivo, oral administration of nepetin suppressed mast cell-dependent PCA reaction in a dose-dependent manner. The results of this study suggest that nepetin might have an anti-allergic potential related to mast cell-mediated inflammatory diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12272-020-01212-7DOI Listing
February 2020

RACK1 promotes cancer progression by increasing the M2/M1 macrophage ratio via the NF-κB pathway in oral squamous cell carcinoma.

Mol Oncol 2020 04 20;14(4):795-807. Epub 2020 Feb 20.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Receptor for activated C kinase 1 (RACK1) has been shown to promote oral squamous cell carcinoma (OSCC) progression, and RACK1 expression levels have been negatively correlated with prognosis in patients with OSCC. Here, we investigated the impact of RACK1 OSCC expression on the recruitment and differentiation of tumor-associated macrophages. High RACK1 expression in OSCC cells correlated with increased M2 macrophage infiltration in tumor samples from a clinical cohort study. Moreover, the combination of RACK1 expression and the M2/M1 ratio could successfully predict prognosis in OSCC. OSCC cells with high RACK1 expression inhibited the migration of THP-1 cells, promoted M2-like macrophage polarization in vitro, and increased the proportion of M2-like macrophages in a xenograft mouse model. Moreover, both M1- and M2-like macrophage polarization-associated proteins were induced in macrophages cocultured with RACK1-silenced cell supernatant. A mechanistic study revealed that the expression and secretion of C-C motif chemokine 2 (CCL2), C-C motif chemokine 5 (CCL5), interleukin-6 (IL-6), and interleukin-1 (IL-1) are closely related to RACK1 expression. In addition, blocking nuclear factor-kappa B (NF-κB) could promote M2-like macrophage polarization. These results indicate that RACK1 and the M2/M1 ratio are predictors of a poor prognosis in OSCC. RACK1 promotes M2-like polarization by regulating NF-κB and could be used as a potential therapeutic target for antitumor immunity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/1878-0261.12644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138402PMC
April 2020

A Characteristic Filtering Method for Pulse Wave Signal Quality Assessment.

Annu Int Conf IEEE Eng Med Biol Soc 2019 Jul;2019:603-606

Pulse wave is an important physiological signal widely used in clinic. In practical applications, the pulse wave recordings are easily corrupted by different interferences. Sometimes, it is very difficult to eliminate the noise by commonly used filtering methods. In this study, we proposed a filtering method based on the characteristics of pulse wave recordings to remove the noisy outliers. Firstly, five characteristics, short-term energy (SE), ascending intensity difference (AID), descending intensity difference (DID), ascending time difference (ATD), and descending time difference (DTD), were chosen as metrics and calculated from cardiac pulse wave. Then the median lines of the five metrics were obtained using a median filter, respectively. An acceptable value range around the median line of each metric was set based on histogram distribution analysis and was used to examine pulse wave recordings cardiac-cycle-by-cycle. For each cardiac cycle, when one or more of its five characteristic values exceed(s) the acceptable range, the pulse wave recording segment was discarded from further analysis. With this proposed method, the noisy outliers could be efficiently identified from the pulse wave recordings. This suggests that the proposed preprocessing method would be useful in improving the assessment performance of pulse-wave-based clinical applications. Additionally, the method might also be extended used in other physiological signals pre-processing, such as ECG, blood pressure wave, etc.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/EMBC.2019.8856811DOI Listing
July 2019

One-pot concomitant preparation of two copper(II) coordination polymers with different configurations of bridging bithiophene ligands.

Acta Crystallogr C Struct Chem 2020 01 1;76(Pt 1):37-43. Epub 2020 Jan 1.

School of Chemical Engineering, Guizhou Minzu University, Guiyang, Guizhou 550025, People's Republic of China.

By employing the conjugated bithiophene ligand 5,5'-bis(1H-imidazol-1-yl)-2,2'-bithiophene (bibp), which can exhibit trans and cis conformations, two different Cu coordination polymers, namely, poly[[μ-5,5'-bis(1H-imidazol-1-yl)-2,2'-bithiophene-κN:N'](μ-4,4'-oxydibenzoato-κO:O')copper(II)], [Cu(CHO)(CHNS)] or [Cu(bibp)(oba)], (I), and catena-poly[μ-aqua-bis[μ-5,5'-bis(1H-imidazol-1-yl)-2,2'-bithiophene-κN:N']bis(μ-4,4'-oxydibenzoato)-κO:O':O'';κO:O',O'':O'-dicopper(II)], [Cu(CHO)(CHNS)(HO)] or [Cu(bibp)(oba)(HO)], (II), have been prepared through one-pot concomitant crystallization and characterized by single-crystal X-ray diffraction, IR spectroscopy, elemental analysis, powder X-ray diffraction (PXRD) and thermogravimetric (TG) analysis. Single-crystal X-ray diffraction indicates that the most interesting aspect of the structure is the existence of sole trans and cis conformations of the bibp ligand in a single net of (I) and (II), respectively. Compound (I) displays a threefold interpenetrating three-dimensional framework with a 4-connected {6.8} cds topology, whereas (II) features a one-dimensional chain structure. In the crystal of (II), the polymeric chains are further extended through C-H...O hydrogen bonds and C-H...π interactions into a three-dimensional supramolecular architecture. In addition, strong intramolecular O-H...O hydrogen bonds formed between the bridging water molecules and the carboxylate O atoms improve the stability of the framework of (II). Furthermore, solid-state UV-Vis spectroscopy experiments show that compounds (I) and (II) exhibit optical band gaps which are characteristic for optical semiconductors, with values of 2.70 and 2.26 eV, respectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1107/S2053229619016024DOI Listing
January 2020

25-Hydroxyvitamin D positively regulates periodontal inflammaging via SOCS3/STAT signaling in diabetic mice.

Steroids 2020 04 7;156:108570. Epub 2020 Jan 7.

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

Background: Diabetes is a known age-related disease. Inflammaging has recently been shown to result in diabetic complications. Vitamin D is related to aging in the latest study but little is known about the underlying mechanism. Here, we investigated the effects of 25-Hydroxyvitamin D (25(OH)D) on inflammaging in diabetic periodontitis, a common chronic inflammatory diabetic complication.

Experimental Design: A model of Porphyromonas gingivalis-infected db/db mice as experimental type 2 diabetic periodontitis was adopted in the whole study. A range of techniques, including microCT, western blotting, ELISA, histological and immunohistochemical analysis, were carried out in this study. The distinctive senescence-associated secretory phenotype (SASP) in serum was measured by Luminex technology.

Results: We found an archetypal inflammaging status occurred in db/db mice. An increased SASP, senescent enhancement, and periodontal destruction were observed in periodontitis-db/db mice. Upon administration with 25(OH)D, periodontitis-db/db mice presented increased levels of serum 25(OH)D, 1α,25-Dihydroxyvitamin D and calcium. Moreover, decreased p16/p21-positive cells, relieved periodontal conditions and ameliorated serum SASP secretion were found in the periodontitis-db/db mice after treatment. Gingival tissue exhibited increased level of VDR and decreased expression of SOCS3, p-STAT3/STAT3, p-STAT5/STAT5, NF-κB and IL-1β, which were consistent with the change of p16/p21 expression.

Conclusion: Diabetic periodontitis appeared to develop an inflammaging status resulted in periodontal infection. 25(OH)D could inhibit SASP secretion through reducing SOCS3 expression in experimental diabetic periodontitis, dependently inactivating NF-κB pro-inflammatory signaling. The reversible effect further documented that the inflammaging might be a highly likely contributor in diabetic periodontitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.steroids.2019.108570DOI Listing
April 2020

Monoaminergic Genetic Variants, Prefrontal Cortex-Amygdala Circuit, and Emotional Symptoms in Children With ADHD: Exploration Based on the Gene-Brain-Behavior Relationship.

J Atten Disord 2020 Jan 8:1087054719897838. Epub 2020 Jan 8.

Peking University Sixth Hospital/Institute of Mental Health, Beijing, China.

This study aimed to explore the association between monoaminergic genetic variants and emotional lability (EL) symptoms in children with ADHD. In addition, genetic effects on prefrontal cortex (PFC)-amygdala functional connectivity (FC) were investigated. Children with ADHD and controls were genotyped for five monoaminergic genetic variants and were evaluated for EL symptoms. Imaging genetic exploration was conducted with previously reported aberrant PFC-amygdala resting-state functional connectivities (RSFCs) as target features. A genotypic effect on EL symptoms was only found for -rs3785143, indicating higher EL symptoms in TT genotype carriers than in C-allele carriers. Imaging genetic analyses indicated a marginal effect of -rs3785143 on ADHD-altered FC between the superficial amygdala (SFA) and middle frontal gyrus (MFG). Mediation analysis suggested potential effects of -rs3785143 via RSFC (SFA-MFG) on EL. variants might participate in the pathogenesis of EL in children with ADHD by influencing the function of the PFC-amygdala circuit.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1087054719897838DOI Listing
January 2020

Towards resolving the co-existing impacts of multiple dynamic factors on the performance of EMG-pattern recognition based prostheses.

Comput Methods Programs Biomed 2020 Feb 17;184:105278. Epub 2019 Dec 17.

CAS Key Laboratory of Human-Machine Intelligence-Synergy Systems, Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), Shenzhen 518055, China; SIAT Branch, Shenzhen Institute of Artificial Intelligence and Robotics for Society, SIAT, CAS Shenzhen 518055, China; Research Center for Neural Engineering, SIAT, CAS, Shenzhen 518055, China. Electronic address:

Background And Objective: Mobility of subject (MoS) and muscle contraction force variation (MCFV) have been shown to individually degrade the performance of multiple degrees of freedom electromyogram (EMG) pattern recognition (PR) based prostheses control systems. Though these factors (MoS-MCFV) co-exist simultaneously in the practical use of the prosthesis, their combined impact on PR-based system has rarely been studied especially in the context of amputees who are the target users of the device.

Methods: To address this problem, this study systematically investigated the co-existing impact of MoS-MCFV on the performance of PR-based movement intent classifier, using EMG recordings acquired from eight participants who performed multiple classes of targeted limb movements across static and non-static scenarios with three distinct muscle contraction force levels. Then, a robust feature extraction method that is invariant to the combined effect of MoS-MCFV, namely, invariant time-domain descriptor (invTDD), was proposed to optimally characterize the multi-class EMG signal patterns in the presence of both factors.

Results: Experimental results consistently showed that the proposed invTDD method could significantly mitigate the co-existing impact of MoS-MCFV on PR-based movement-intent classifier with error reduction in the range of 7.50%~17.97% (p<0.05), compared to the commonly applied methods. Further evaluation using 2-dimentional principal component analysis (PCA) technique, revealed that the proposed invTDD method has obvious class-separability in the PCA feature space, with a significantly lower standard error (0.91%) compared to the existing methods.

Conclusion: This study offers compelling insight on how to develop accurately robust multiple degrees of freedom control scheme for multifunctional prostheses that would be clinically viable. Also, the study may spur positive advancement in other application areas of medical robotics that adopts myoelectric control schemes such as the electric wheelchair and human-computer-interaction systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cmpb.2019.105278DOI Listing
February 2020

Dual-functional guanosine-based hydrogel integrating localized delivery and anticancer activities for cancer therapy.

Biomaterials 2020 02 3;230:119598. Epub 2019 Nov 3.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, PR China. Electronic address:

Supramolecular hydrogel delivery systems have attracted widely attention owing to incorporating various therapeutic agents in carriers to decrease unpredictable toxicities, improve curative efficacy, and protect drug bioactivity. Nonetheless, the dual-functional supramolecular hydrogel integrating localized delivery and antineoplastic activities in one system have rarely observed. In this study, we successfully developed a novel supramolecular hydrogel, isoguanosine-borate-guanosine (isoGBG), with reversibly and dynamic borate ester bonds formed via boric acids and diols derived from nature products guanosine and isoguanosine in one pot by following a simple procedure. Both in vivo and in vitro results demonstrated that the isoGBG hydrogel not only displays excellent stability, self-healing properties and biocompatibility, but also has highly anti-tumor activities through inducing tumor cell apoptosis and excellent inhibition effect of tumor recurrence. These findings suggested that isoGBG hydrogel can serve as a dual-function hydrogel system integrating drug carrier and anti-cancer compound in one system, which provided a promising strategy for the design of functional supramolecular hydrogel in the local management of cancer in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biomaterials.2019.119598DOI Listing
February 2020