Publications by authors named "Jianping Liu"

477 Publications

Mesenchymal Stem Cells: An Excellent Candidate for the Treatment of Diabetes Mellitus.

Int J Endocrinol 2021 28;2021:9938658. Epub 2021 May 28.

Department of Endocrinology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.

Mesenchymal stem cells (MSCs) are adult stem cells (ASCs) known for repairing damaged cells, exerting anti-inflammatory responses and producing immunoregulatory effects that can be significantly induced into insulin-producing cells (IPCs), providing an inexhaustible supply of functional cells for cell replacement therapy and disease modeling for diabetes. MSC therapy may be the most promising strategy for diabetes mellitus because of these significant merits. In this paper, we focused on MSC therapy for diabetes.
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http://dx.doi.org/10.1155/2021/9938658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178013PMC
May 2021

Classical swine fever virus infection suppresses claudin-1 expression to facilitate its replication in PK-15 cells.

Microb Pathog 2021 Aug 29;157:105012. Epub 2021 May 29.

College of Animal Veterinary Medicine, Yunnan Agricultural University, Kunming, 650201, Yunnan, China. Electronic address:

Classical swine fever (CSF) is one of the most epidemic viral diseases in swine industry. The causative pathogen is CSF virus (CSFV), a small enveloped RNA virus of Flaviviridae family. Claudin-1 was reported to be involved in the infections of a number of viruses, including many from Flaviviridae family, but no studies have investigated the role of porcine claudin-1 during CSFV infection in PK-15 cells. In this study, on the one hand, we demonstrated that CSFV infection reduced the claudin-1 expression at both mRNA and protein levels; on the other hand, CSFV infection was enhanced after claudin-1 knockdown, but inhibited by claudin-1 overexpression in a dose-dependent manner. Furthermore, negative correlation was demonstrated between the claudin-1 expression and CSFV titer. In conclusion, claudin-1 might be a barrier for CSFV infection in PK-15 cells, while CSFV bypasses the barrier through lysosome mediated degradation of claudin-1, which could be repressed by bafilomycin A1. Although the elaborate mechanisms how claudin-1 plays its roles in CSFV infection require further investigations, this study may advance our understanding of the molecular host-pathogen interaction mechanisms underlying CSFV infection and suggests enhancement of porcine claudin-1 as a potential preventive or therapeutic strategy for CSF control.
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http://dx.doi.org/10.1016/j.micpath.2021.105012DOI Listing
August 2021

Efficient Construction of 5H-1,4-Benzodiazepine Derivatives by a Catalyst-Free Direct Aerobic Oxidative Annulation Strategy.

ChemSusChem 2021 May 31. Epub 2021 May 31.

School of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, Jiangsu, 225002, P. R. China.

A catalyst-free direct aerobic oxidative annulation reaction of 2-aminobenzylic amines and α-hydroxy ketones efficiently afforded versatile 5H-1,4-benzodiazepine derivatives by employing air as economic and green oxidant under mild conditions. Interestingly, solvent was found to be crucial to the reaction, so that by using acetic acid as the best solvent an efficient and practical method could be achieved, requiring no catalysts or additives at all. This method tolerates a wide range of 2-aminobenzylic amines and α-hydroxy ketones and could be scaled up to multigram synthesis and directly applied in one-step synthesis of the pharmaceutically active N-desmethylmedazepam derivatives, revealing the potential of this new method in the synthesis of 5H-1,4-benzodiazepine skeleton-based pharmaceuticals and chemicals.
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http://dx.doi.org/10.1002/cssc.202100703DOI Listing
May 2021

Heat/pH-boosted release of 5-fluorouracil and albumin-bound paclitaxel from Cu-doped layered double hydroxide nanomedicine for synergistical chemo-photo-therapy of breast cancer.

J Control Release 2021 May 12;335:49-58. Epub 2021 May 12.

Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD 4072, Australia. Electronic address:

Considerable attention has been devoted to nanomedicine development for breast cancer therapy, while the therapeutic efficiency is far from satisfactory owing to non-specific biodistribution-caused side effects and limitation of single modal treatment. In this study, we have developed a novel nanomedicine for efficient combination breast cancer therapy. This nanomedicine was based on copper-doped layered double hydroxide (Cu-LDH) nanoparticles loaded with two FDA-approved anticancer drugs, i.e. 5-fluorouracil (5-FU) and albumin-bound paclitaxel (nAb-PTX) with complementary chemotherapeutic actions. The 5-FU/[email protected] nanomedicine showed pH-sensitive heat-facilitated therapeutic on-demand release and demonstrated the moderate-to-strong synergy of photothermal therapy and chemotherapy in inducing apoptosis of breast cancer cells (4 T1). This nanomedicine had a high colloidal stability in saline and serum, and efficiently accumulated in the tumor tissue. Remarkably, this nanomedicine nearly eliminated 4 T1 tumors in vivo after a two-course treatment under mild 808 nm laser irradiation (0.75 W/cm, 3 min) at very low doses of 5-FU and nAb-PTX (0.25 and 0.50 mg/kg, 8-50 times less than that used in other nanoformulations), without observable side effects. Therefore, this research provides a novel approach to designing multifunctional nanomedicines for on-demand release of chemotherapeutics to cost-effectively treat breast cancer with minimal side effects in future clinic applications.
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http://dx.doi.org/10.1016/j.jconrel.2021.05.011DOI Listing
May 2021

Development of potent and selective inhibitors targeting the papain-like protease of SARS-CoV-2.

Cell Chem Biol 2021 Jun 27;28(6):855-865.e9. Epub 2021 Apr 27.

Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China. Electronic address:

The COVID-19 pandemic has been disastrous to society and effective drugs are urgently needed. The papain-like protease domain (PLpro) of SARS-CoV-2 (SCoV2) is indispensable for viral replication and represents a putative target for pharmacological intervention. In this work, we describe the development of a potent and selective SCoV2 PLpro inhibitor, 19. The inhibitor not only effectively blocks substrate cleavage and immunosuppressive function imparted by PLpro, but also markedly mitigates SCoV2 replication in human cells, with a submicromolar IC. We further present a convenient and sensitive activity probe, 7, and complementary assays to readily evaluate SCoV2 PLpro inhibitors in vitro or in cells. In addition, we disclose the co-crystal structure of SCoV2 PLpro in complex with a prototype inhibitor, which illuminates their detailed binding mode. Overall, these findings provide promising leads and important tools for drug discovery aiming to target SCoV2 PLpro.
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http://dx.doi.org/10.1016/j.chembiol.2021.04.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075810PMC
June 2021

An RNAi Screening of Clinically Relevant Transcription Factors Regulating Human Adipogenesis and Adipocyte Metabolism.

Endocrinology 2021 Jul;162(7)

Lipid laboratory, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, SE-14186, Sweden.

Context: Healthy hyperplasic (many but smaller fat cells) white adipose tissue (WAT) expansion is mediated by recruitment, proliferation and/or differentiation of new fat cells. This process (adipogenesis) is controlled by transcriptional programs that have been mostly identified in rodents.

Objective: A systemic investigation of adipogenic human transcription factors (TFs) that are relevant for metabolic conditions has not been revealed previously.

Methods: TFs regulated in WAT by obesity, adipose morphology, cancer cachexia, and insulin resistance were selected from microarrays. Their role in differentiation of human adipose tissue-derived stem cells (hASC) was investigated by RNA interference (RNAi) screen. Lipid accumulation, cell number, and lipolysis were measured for all screened factors (148 TFs). RNA (RNAseq), protein (Western blot) expression, insulin, and catecholamine responsiveness were examined in hASC following siRNA treatment of selected target TFs.

Results: Analysis of TFs regulated by metabolic conditions in human WAT revealed that many of them belong to adipogenesis-regulating pathways. The RNAi screen identified 39 genes that affected fat cell differentiation in vitro, where 11 genes were novel. Of the latter JARID2 stood out as being necessary for formation of healthy fat cell metabolic phenotype by regulating expression of multiple fat cell phenotype-specific genes.

Conclusion: This comprehensive RNAi screening in hASC suggests that a large proportion of WAT TFs that are impacted by metabolic conditions might be important for hyperplastic adipose tissue expansion. The screen also identified JARID2 as a novel TF essential for the development of functional adipocytes.
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http://dx.doi.org/10.1210/endocr/bqab096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197287PMC
July 2021

3D heterospecies spheroids of pancreatic stroma and cancer cells demonstrate key phenotypes of pancreatic ductal adenocarcinoma.

Transl Oncol 2021 Jul 1;14(7):101107. Epub 2021 May 1.

Pancreas Cancer Research Lab, Department of Clinical Science, Intervention and Technology, (CLINTEC), Karolinska Institutet, Huddinge SE 141 86, Sweden. Electronic address:

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, partly due to the dense desmoplasia and a lack of suitable model systems to study. In the present work, we developed a 3D heterospecies spheroid model to study the microenvironmental interactions between tumor cells and stellate cells which can also be employed to test therapeutic regimens. We set up monospheroids and heterospheroids made up from murine pancreatic stellate cells (mPSCs) and human PDAC cells (Panc1), which allowed for direct isolation of mRNA from a mixed cell population followed by an in silico separation of the RNA-seq reads. Global transcript level changes for cells in heterospheroids versus monospheroids were calculated, followed by gene set enrichment analysis and molecular subtype analysis. We observed an apparent shift of Panc1 from the classical to the squamous/basal-like phenotype upon co-culture with mPSCs. Moreover, mPSCs acquired a different cancer-associated fibroblast-related phenotype upon co-culture with Panc1. We analyzed the tumor cell-specific chemosensitivities towards gemcitabine, paclitaxel and SN38 and compared these to published pharmacotranscriptomic signatures. In conclusion, our heterospecies spheroid model reflected key aspects of PDAC and facilitated the study of intercellular interactions between tumor and stroma while additionally proving to be a good model for studying therapeutic responses.
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http://dx.doi.org/10.1016/j.tranon.2021.101107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111319PMC
July 2021

Effect of Graded-Indium-Content Superlattice on the Optical and Structural Properties of Yellow-Emitting InGaN/GaN Quantum Wells.

Materials (Basel) 2021 Apr 9;14(8). Epub 2021 Apr 9.

Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China.

We have improved the material quality of the high indium composition InGaN/GaN multiple quantum wells (MQWs) grown on free-standing GaN substrates using the graded-indium-content superlattice. We found that by adopting a graded-indium-content superlattice structure, the spectral FWHM of the yellow emitting InGaN/GaN MQW was reduced from 181 meV to 160 meV, and the non-radiative recombination lifetime increased from 13 ns to 44 ns. Besides, the graded-indium-content superlattice can mitigate strain relaxation in high indium composition MQWs as shown by the TEM diffraction patterns.
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http://dx.doi.org/10.3390/ma14081877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069205PMC
April 2021

A Novel Method for Estimating and Balancing the Second Harmonic Error of Cylindrical Fused Silica Resonators.

Micromachines (Basel) 2021 Apr 1;12(4). Epub 2021 Apr 1.

College of Advanced Interdisciplinary Studies, National University of Defense Technology, Changsha 410073, China.

The cylindrical resonator gyroscope (CRG) is a type of Coriolis vibratory gyroscope which measures the angular velocity or angle through the precession of the elastic wave of the cylindrical resonator. The cylindrical fused silica resonator is an essential component of the CRG, the symmetry of which determines the bias drift and vibration stability of the gyroscope. The manufacturing errors breaking the symmetry of the resonator are usually described by Fourier series, and most studies are only focusing on analyzing and reducing the fourth harmonic error, the main error source of bias drift. The second harmonic error also is one of the obstacles for CRG towards high precision. Therefore, this paper provides a chemical method to evaluate and balance the second harmonic error of cylindrical fused silica resonators. The relation between the frequency split of the = 1 mode and the second harmonic error of the resonator is obtained. Simulations are performed to analyze the effects of the first three harmonic errors on the frequency splits. The relation between the location of the low-frequency axis of = 1 mode and the heavy axis of the second harmonic error is also analyzed by simulation. Chemical balancing experiments on two fused silica resonators demonstrate the feasibility of this balancing procedure, and show good consistency with theoretical and simulation analysis. The second harmonic error of the two resonators is reduced by 86.6% and 79.8%, respectively.
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http://dx.doi.org/10.3390/mi12040380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066539PMC
April 2021

Association of Etoricoxib treatment and incident hypoxia in patients with aortic dissection undergoing endovascular aortic repair.

Biomed Pharmacother 2021 Jul 23;139:111625. Epub 2021 Apr 23.

Department of Cardiology, The Third People's Hospital of Huizhou, The Affiliated Hospital of Guangzhou Medical University, Huizhou, Guangdong, China. Electronic address:

Objective: The current study was to evaluate the association of Etoricoxib treatment and incident hypoxia among type-B aortic dissection (AD) patients undergoing endovascular aortic repair (EVAR).

Methods: Patients undergoing EVAR were retrospectively recruited. Based on Etoricoxib use, patients were divided into the non-treated and Etoricoxib-treated groups. Baseline characteristics including demographics, laboratory parameters, characteristics of aortic computer tomography and echocardiography, medications used, and procedural characteristics were collected from the electronic health record.

Results: Compared to non-treated group (n = 36), prevalence of obesity and fever at baseline was higher in Etoricoxib-treated group (n = 24; P < 0.05). Mean number of neutrophils, and mean serum CRP and D-dimer levels were higher in Etoricoxib-treated group (P < 0.05). The overall incidence of hypoxia was lower in Etoricoxib-treated group (44.4% vs 33.4%, P < 0.05). Increase in neutrophils count, serum CRP and D-dimer levels was associated with incident hypoxia, with an odds ratio (OR) of 1.36 (95% confidence interval [CI] 1.07-1.65), 1.44 (95% CI 1.12-1.78) and 1.25 (95% CI 1.01-1.47) respectively. In unadjusted model, Etoricoxib use was associated with a 44% lower odds of incident hypoxia. After adjustment for inflammatory markers, the association between Etoricoxib and incident hypoxia was non-significant, with OR of 0.95% and 95% CI of 0.78-1.06.

Conclusion: Compared to patients who did not receive Etoricoxib during hospitalization, those treated with Etoricoxib had lower incidence of hypoxia, which might be attributed to its anti-inflammatory effects.
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http://dx.doi.org/10.1016/j.biopha.2021.111625DOI Listing
July 2021

Probing Dynamic Behavior of Chemical Enhancers Passing In and Out of the Stratum Corneum and Modulation by Biodegradable Enhancer.

AAPS PharmSciTech 2021 Apr 20;22(4):139. Epub 2021 Apr 20.

Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing, 211198, People's Republic of China.

Chemical enhancers (CEs) decreased the barrier of the stratum corneum (SC) to enhance drug permeation. This was a "dynamic" behavior, which involved three processes including passing in, acting on, and passing out of the SC. However, compared with mature "static" researches about acting on the SC, the other two processes were poorly understood. This work aimed to probe the dynamic behavior of CEs and modulate it for satisfactory effectiveness. The investigating method of CEs' dynamic behavior was established to obtain the rate of CEs passing in and out of the SC. An analysis attribution was conducted to obtain the possible reasons for the quite different dynamic behavior of CEs based on log P, solubility parameter, and minimum binging energy. It demonstrated the rate of CEs passing in and out of the SC was dependent on CE affinity with the SC and the interaction between CEs and the SC, respectively. The relevance between CEs' dynamic behavior and the extent of decreasing SC barrier was confirmed by transepidermal water loss (TEWL). The higher rate of CE passing in the SC and a lower rate of passing out of the SC may contribute to an increased concentration of CEs in the SC, leading to a stronger ability to decrease the SC barrier. More importantly, two biodegradable CEs (Leu-Dod and Ser-Dod) of dodecanol were synthesized and achieved a modulation of its dynamic behavior to obtain more satisfactory effectiveness of enhancing drug permeation. This work was meaningful for the guidance of rationally promoting CEs' effectiveness from a dynamic perspective, which was an unprecedented attempt in this field.
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http://dx.doi.org/10.1208/s12249-021-02009-7DOI Listing
April 2021

Effects of Different Ambient Temperatures on Caecal Microbial Composition in Broilers.

Pol J Microbiol 2021 Mar 9;70(1):33-43. Epub 2021 Mar 9.

Yunnan Provincial Key Laboratory of Animal Nutrition and Feed Science, Faculty of Animal Science and Technology, Yunnan Agricultural University, Kunming, The People's Republic of China.

Short-term or acute temperature stress affect the immune responses and alters the gut microbiota of broilers, but the influences of long-term temperature stress on stress biomarkers and the intestinal microbiota remains largely unknown. Therefore, we examined the effect of three long-term ambient temperatures (high (HC), medium (MC), and low (LC) temperature groups) on the gene expression of broilers' heat shock proteins (Hsps) and inflammation - related genes, as well as the caecal microbial composition. The results revealed that Hsp70 and Hsp90 levels in HC group significantly increased, and levels of Hsp70, Hsp90, IL-6, TNF-α, and NFKB1 in LC group were significantly higher than in MC group ( < 0.05). In comparison with the MC group, the proportion of Firmicutes increased in HC and LC groups, while that of Bacteroidetes decreased in LC group at phylum level ( < 0.05). At genus level, the proportion of /,and increased in HC group; the fraction of was higher in LC group; and the percentage of and decreased in both HC and LC groups ( < 0.05). Functional analysis based on communities' phylogenetic investigation revealed that the pathways involved in environmental information processing and metabolism were enriched in the HC group. Those involved in cellular processes and signaling, metabolism, and gene regulation were enriched in LC group. Hence, we conclude that the long-term temperature stress can greatly alter the intestinal microbial communities in broilers and may further affect the host's immunity and health.
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http://dx.doi.org/10.33073/pjm-2021-001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008768PMC
March 2021

Indole Inhibits IncP-1 Conjugation System Mainly Through Promoting and Expression.

Front Microbiol 2021 19;12:628133. Epub 2021 Mar 19.

Department of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.

Indole works as an interspecies signal molecule to regulate multiple physiological activities, like antibiotic resistance, acid resistance, and virulence. However, the effect of indole on conjugation is unknown. Here, with λπ as a donor strain that carries a chromosomally integrated conjugative RP4 plasmid, we explored the effect of indole on conjugation of a mobilizable pUCP24T plasmid imparting gentamycin resistance. The results showed that exogenous indole treatment inhibited conjugative transfer of pUCP24T from λπ to recipient strains, and . Furthermore, raising endogenous indole production through overexpression of TnaA, a tryptophanase, in λπ significantly inhibited both λπ- and λπ- conjugation, whereas deficiency of reversed the phenotype. Subsequent mechanistic studies revealed that exogenous indole significantly inhibited the expression of mating pair formation gene () and the DNA transfer and replication gene (), mainly due to the promotion of regulatory genes ( and ), and the result was confirmed in knockout and overexpression strains. Additionally, we found that both extracellular indole production and expression of λπ were downregulated by ciprofloxacin (CIP). Intriguingly, one-eighth minimum inhibitory concentration of CIP treatment clearly facilitated both λπ- and λπ- conjugation, and indole inhibited CIP-induced conjugation frequency. These data suggest that indole may play a negative role in the process of CIP-induced conjugation. This is the first study to reveal the biological function of indole-inhibiting conjugation and its role in CIP-induced conjugation, which may be developed into a new way of controlling the spread of antibiotic resistance.
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http://dx.doi.org/10.3389/fmicb.2021.628133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017341PMC
March 2021

A human cell type similar to murine central nervous system perivascular fibroblasts.

Exp Cell Res 2021 May 31;402(2):112576. Epub 2021 Mar 31.

Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden. Electronic address:

The brain vasculature has several specific features, one of them being the blood-brain barrier (BBB), which supports and protects the brain by allowing for the passage of oxygen and nutrients, while at the same time preventing passage of pathogens and toxins. The BBB also prevents efficient delivery of drugs to the brain, e.g. for treatment of brain tumors. In the murine brain, perivascular fibroblasts were recently identified as a novel potential constituent of the BBB. Here we present the existence of human cells that could be the equivalent to the murine brain perivascular fibroblasts. Using RNA sequencing, we show a similar transcriptomic profile of cultured human brain cells and murine perivascular fibroblasts. These data open up a window for new hypotheses on cell types involved in human CNS diseases.
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http://dx.doi.org/10.1016/j.yexcr.2021.112576DOI Listing
May 2021

Human growth hormone proteoform pattern changes in pituitary adenomas: Potential biomarkers for 3P medical approaches.

EPMA J 2021 Mar 3;12(1):67-89. Epub 2021 Mar 3.

Science and Technology Innovation Center, Shandong First Medical University, 6699 Qingdao Road, Jinan, Shandong 250117 People's Republic of China.

Relevance: Human growth hormone (hGH) is synthesized, stored, and secreted by somatotroph cells in the pituitary gland, and promotes human growth and metabolism. Compared to a normal pituitary, a GH-secreting pituitary adenoma can secrete excessive GH to cause pathological changes in body tissues. GH proteoform changes would be associated with GH-related disease pathogenesis.

Purpose: This study aimed to elucidate changes in GH proteoforms between GH-secreting pituitary adenomas and control pituitaries for the predictive diagnostics, targeted prevention, and personalization of medical services.

Methods: The isoelectric point (pI) and relative molecular mass (Mr) are two basic features of a proteoform that can be used to effectively array and detect proteoforms with two-dimensional gel electrophoresis (2DGE) and 2DGE-based western blot. GH proteoforms were characterized with liquid chromatography (LC) and mass spectrometry (MS). Phosphoproteomics, ubiquitinomics, acetylomics, and bioinformatics were used to analyze post-translational modifications (PTMs) of GH proteoforms in GH-secreting pituitary adenoma tissues and control pituitaries.

Results: Sixty-six 2D gel spots were found to contain hGH, including 46 spots (46 GH proteoforms) in GH-secreting pituitary adenomas and 35 spots (35 GH proteoforms) in control pituitaries. Further, 35 GH proteoforms in control pituitary tissues were matched with 35 of 46 GH proteoforms in GH-secreting pituitary adenoma tissues; and 11 GH proteoforms were presented in only GH-secreting pituitary adenoma tissues but not in control pituitary tissues. The matched 35 GH proteoforms showed quantitative changes in GH-secreting pituitary adenomas compared to the controls. The quantitative levels of those 46 GH proteoforms in GH-secreting pituitary adenomas were significantly different from those 35 GH proteoforms in control pituitaries. Meanwhile, different types of PTMs were identified among those GH proteoforms. Phosphoproteomics identified phosphorylation at residues Ser77, Ser132, Ser134, Thr174, and Ser176 in hGH. Ubiquitinomics identified ubiquitination at residue Lys96 in hGH. Acetylomics identified acetylation at reside Lys171 in hGH. Deamination was identified at residue Asn178 in hGH.

Conclusion: These findings provide the first hGH proteoform pattern changes in GH-secreting pituitary adenoma tissues compared to control pituitary tissues, and the status of partial PTMs in hGH proteoforms. Those data provide in-depth insights into biological roles of hGH in GH-related diseases, and identify hGH proteoform pattern biomarkers for treatment of a GH-secreting pituitary adenoma in the context of 3P medicine -predictive diagnostics, targeted prevention, and personalization of medical services.

Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-021-00232-7.
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http://dx.doi.org/10.1007/s13167-021-00232-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954920PMC
March 2021

Morphology/Interstitial Fluid Pressure-Tunable Nanopomegranate Designed by Alteration of Membrane Fluidity under Tumor Enzyme and PEGylation.

Mol Pharm 2021 05 26;18(5):2039-2052. Epub 2021 Mar 26.

School of Pharmacy, China Pharmaceutical University, No. 639, Longmian Road, Nanjing 210009, PR China.

Up to now, insufficient drug accumulation in tumor remains a major challenge for nanochemotherapy. However, the spherical nanocarriers with large diameter, which are beneficial for blood circulation and tumor extravasation, cannot travel deep in a tumor. Additionally, high tumor interstitial fluid pressure (IFP) in the tumor microenvironment may promote the efflux of the penetrable nanodrugs. Therefore, the size and shape of nanocarriers as well as the tumoral IFP can be regulated synchronously for improved tumor penetration and combined chemotherapy. Herein, a novel dual-functional polymer-polypeptide (Biotin-PEG-GKGPRQITITK) for both verified tumor targeting and responsiveness was synthesized to construct the "peel" of nanopomegranate-like nanovectors (DI-MPL), in which docetaxel-loaded micelles was encapsulated as "seeds". Interestingly, DI-MPL was endowed multi-abilities of tunable size/shape switch and controlled release of IFP alleviator imatinib (IM), which were developed with one and the same strategy-alteration of membrane fluidity under the cleavage of polymer-polypeptide and PEGylation. As a result, the peel of DI-MPL could turn into small pieces with the seed scattered out in response to matrix metalloproteinase-9 (MMP-9), making nanopomegranate (180 nm) switch into spheres/disks (40 nm), during which IM is released to reduce IFP synchronously. With prominent tumor penetration ability in both multicellular tumor spheroids (MCTS) and tumor tissue, DI-MPL exhibited optimal inhibition of MCTS growth and the enhanced chemotherapy in comparison to other preparations. Meanwhile, the improved penetrability of DI-MPL in tumor tissue was found to be related to the reduced IFP, which is achieved via inhibiting expression of phosphorylated platelet-derived growth factor receptor-β (-PDGFR-β) by IM. Altogether, the bilateral adjusting strategies from nanocarrier size/shape and tumoral IFP with a single enzyme-responsive material could provide a potential combined chemotherapy to improve tumor penetration.
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http://dx.doi.org/10.1021/acs.molpharmaceut.1c00036DOI Listing
May 2021

Neuronal cell-based high-throughput screen for enhancers of mitochondrial function reveals luteolin as a modulator of mitochondria-endoplasmic reticulum coupling.

BMC Biol 2021 03 24;19(1):57. Epub 2021 Mar 24.

Center for Alzheimer Research, Division of Neurogeriatrics, Department of Neurobiology Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.

Background: Mitochondrial dysfunction is a common feature of aging, neurodegeneration, and metabolic diseases. Hence, mitotherapeutics may be valuable disease modifiers for a large number of conditions. In this study, we have set up a large-scale screening platform for mitochondrial-based modulators with promising therapeutic potential.

Results: Using differentiated human neuroblastoma cells, we screened 1200 FDA-approved compounds and identified 61 molecules that significantly increased cellular ATP without any cytotoxic effect. Following dose response curve-dependent selection, we identified the flavonoid luteolin as a primary hit. Further validation in neuronal models indicated that luteolin increased mitochondrial respiration in primary neurons, despite not affecting mitochondrial mass, structure, or mitochondria-derived reactive oxygen species. However, we found that luteolin increased contacts between mitochondria and endoplasmic reticulum (ER), contributing to increased mitochondrial calcium (Ca) and Ca-dependent pyruvate dehydrogenase activity. This signaling pathway likely contributed to the observed effect of luteolin on enhanced mitochondrial complexes I and II activities. Importantly, we observed that increased mitochondrial functions were dependent on the activity of ER Ca-releasing channels inositol 1,4,5-trisphosphate receptors (IPRs) both in neurons and in isolated synaptosomes. Additionally, luteolin treatment improved mitochondrial and locomotory activities in primary neurons and Caenorhabditis elegans expressing an expanded polyglutamine tract of the huntingtin protein.

Conclusion: We provide a new screening platform for drug discovery validated in vitro and ex vivo. In addition, we describe a novel mechanism through which luteolin modulates mitochondrial activity in neuronal models with potential therapeutic validity for treatment of a variety of human diseases.
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http://dx.doi.org/10.1186/s12915-021-00979-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989211PMC
March 2021

The effect of carbonyl on the isomerization of a galanthan ring system and total synthesis of (±)-β-lycorane.

Org Biomol Chem 2021 03 10;19(12):2767-2772. Epub 2021 Mar 10.

School of Pharmaceutical Sciences and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan 650500, P. R. China.

Lycorine-type alkaloids are privileged structures in drug development due to their attractive biological activities. In this paper, the carbonyl on the C ring was proved to have played a critical role in stereoselectivity during the synthesis process, and the galanthan skeleton with a cis-B/C ring is more thermodynamically stable in its presence. Furthermore, the total synthesis of (±)-β-lycorane was successfully completed by employing the Michael addition reaction to construct the galanthan skeleton with a trans-B/C ring. This system might be applied to other structural types with similar stereochemistry setting.
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http://dx.doi.org/10.1039/d0ob02398aDOI Listing
March 2021

MiR-363-3p attenuates neonatal hypoxic-ischemia encephalopathy by targeting DUSP5.

Neurosci Res 2021 Mar 17. Epub 2021 Mar 17.

Department of Paediatrics, Taizhou People's Hospital, Taizhou 225300, Jiangsu, China.

Neonatal hypoxic-ischemia encephalopathy (HIE) refers to hypoxic-ischemic brain damage caused by perinatal asphyxia. Increasing evidence has revealed the crucial roles of microRNAs (miRNAs) in neonatal HIE. In the current research, we aimed to explore the biological role of miR-363-3p in neonatal HIE. For this purpose, we established in vitro models of PC-12 and SH-SY5Y cells subjected to oxygen-glucose deprivation and reperfusion (OGD/R) and an in vivo rat model subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) treatment. First, using H&E staining, TTC staining, and western blot analysis, we observed that DUSP5 knockdown suppressed HIE in vivo. Then, by performing flow cytometric analysis, western blotting, RT-qPCR, and MTT assays, we observed that DUSP5 silencing suppressed OGD/R-induced cell injury in vitro. Subsequently, we explored the potential regulatory mechanism of DUSP5 in OGD/R-treated cells with luciferase reporter assays and RT-qPCR analysis. The results demonstrated that DUSP5 was targeted by miR-363-3p. Next, functional assays, including flow cytometric analysis, MTT assays, western blotting and RT-qPCR, were conducted to explore the biological functions of miR-363-3p in SH-SY5Y and PC-12 cells. Our data showed that miR-363-3p overexpression suppressed OGD/R-induced cell injury. Finally, the results from rescue experiments showed that enhanced DUSP5 expression counteracted the effect of miR-363-3p overexpression. In conclusion, our data suggested that miR-363-3p attenuates neonatal HIE by targeting DUSP5.
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http://dx.doi.org/10.1016/j.neures.2021.03.003DOI Listing
March 2021

High Expression of LINC01268 is Positively Associated with Hepatocellular Carcinoma Progression via Regulating MAP3K7.

Onco Targets Ther 2021 8;14:1753-1769. Epub 2021 Mar 8.

Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, 110001, People's Republic of China.

Objective: As one of the most common neoplastic diseases, hepatocellular carcinoma (HCC) has a high morbidity and mortality, which seriously threatens human health and places a heavy burden on society and medical care. At present, effective early diagnosis, prognosis and treatment of HCC are limited. Altered gene expression patterns of lncRNA are associated with the occurrence, development and prognosis of various malignancies, including HCC. The aim of this study was to investigate the correlation between the expression of LINC01268 and HCC, and to elucidate the potential underlying molecular mechanism.

Methods: Expression level and localization of LINC01268 in human liver cancer cells and HCC tissues were investigated using RT-qPCR and fluorescent in situ hybridization (FISH), respectively. Correlation of expression levels of LINC01268 and MAP3K7 with differentiation and poor overall patient survival of HCC were analyzed using in house collected and publicly available HCC tissue data. RT-qPCR and Western blot were applied to inspect the effects of depletion and overexpression of LINC01268 on MAP3K7 expression. HCC cell proliferation and apoptosis were also investigated by simultaneous overexpression of LINC01268 and knockdown of MAP3K7, in order to delineate that MAP3K7 is a downstream effector of LINC01268.

Results: In this study, we identified that LINC01268 was highly expressed in HCC cell lines and tissues. High LINC01268 expression level was associated with lower HCC nodule number, moderate/poor differentiation and poor overall survival. Knockdown of LINC01268 inhibited the proliferation of HCC cells, which was enhanced by overexpression of LINC01268. Co-expression analysis implied an interaction between LINC01268 and MAP3K7. Similar to LINC01268, MAP3K7 was highly expressed in HCC cells, and positively correlated with moderate/poor differentiation as well as poor prognosis. Knockdown of LINC01268 in HCC cell lines led to reduction of MAP3K7 at both mRNA and protein levels. Phenotypic effects due to LINC01268 overexpression in HCC cells were reversed by knockdown of MAP3K7.

Conclusion: Taken together, the abnormal high expression of LINC01268 is associated with HCC progression via regulating MAP3K7, suggesting LINC01268 as a novel marker for HCC prognosis and potentially a new therapeutic target.
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http://dx.doi.org/10.2147/OTT.S295814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954037PMC
March 2021

Phosphorylation regulates the binding of autophagy receptors to FIP200 Claw domain for selective autophagy initiation.

Nat Commun 2021 03 10;12(1):1570. Epub 2021 Mar 10.

State Key Laboratory of Bioorganic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.

The ULK complex initiates the autophagosome formation, and has recently been implicated in selective autophagy by interacting with autophagy receptors through its FIP200 subunit. However, the structural mechanism underlying the interactions of autophagy receptors with FIP200 and the relevant regulatory mechanism remain elusive. Here, we discover that the interactions of FIP200 Claw domain with autophagy receptors CCPG1 and Optineurin can be regulated by the phosphorylation in their respective FIP200-binding regions. We determine the crystal structures of FIP200 Claw in complex with the phosphorylated CCPG1 and Optineurin, and elucidate the detailed molecular mechanism governing the interactions of FIP200 Claw with CCPG1 and Optineurin as well as their potential regulations by kinase-mediated phosphorylation. In addition, we define the consensus FIP200 Claw-binding motif, and find other autophagy receptors that contain this motif within their conventional LC3-interacting regions. In all, our findings uncover a general and phosphoregulatable binding mode shared by many autophagy receptors to interact with FIP200 Claw for autophagosome biogenesis, and are valuable for further understanding the molecular mechanism of selective autophagy.
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http://dx.doi.org/10.1038/s41467-021-21874-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946963PMC
March 2021

Small molecule screening identified cepharanthine as an inhibitor of porcine reproductive and respiratory syndrome virus infection in vitro by suppressing integrins/ILK/RACK1/PKCα/NF-κB signalling axis.

Vet Microbiol 2021 Apr 17;255:109016. Epub 2021 Feb 17.

College of Animal Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, Yunnan, China. Electronic address:

Porcine Reproductive and Respiratory Syndrome (PRRS) is a devastating disease among the most notorious threats to the swine industry worldwide and is characterized by respiratory distress and reproductive failure. Highly evolving porcine reproductive and respiratory syndrome virus (PRRSV) strains with complicated genetic diversity make the current vaccination strategy far from cost-effective and thus urge identification of potent lead candidates to provide prevention and treatment approaches. From an in vitro small molecule screening with the TargetMol Natural Compound Library comprising 623 small molecules, cytopathic effect (CPE) observations and RT-qPCR analysis of viral ORF7 gene expression identified cepharanthine (CEP) to be one of the most protent inhibitors of PRRSV infection in Marc-145 cells. When compared with tilmicosin, which is one of the most commonly used antibiotics in swine industry to inhibit infections, CEP more prominently inhibited PRRSV infection represented by both RNA and protein levels, further reduced the TCID by 5.6 times, and thus more remarkably protected Marc-145 cells against PRRSV infection. Mechanistically, western blot analyses of the Marc-145 cells and the porcine alveolar macrophages (PAMs) with or without CEP treatment and PRRSV infection at various time points revealed that CEP can inhibit the expression of integrins β1 and β3, integrin-linked kinase (ILK), RACK1 and PKCα, leading to NF-κB suppression and consequent alleviation of PRRSV infection. Collectively, our small molecule screening identified cepharanthine as an inhibitor of PRRSV infection in vitro by suppressing Integrins/ILK/RACK1/PKCα/NF-κB signalling axis, which may enlighten the deeper understanding of the molecular pathogenesis of PRRSV infection and more importantly, suggested CEP as a potential promising drug for PRRS control in veterinary clinics.
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http://dx.doi.org/10.1016/j.vetmic.2021.109016DOI Listing
April 2021

Enhancing Tumor Accumulation and Cellular Uptake of Layered Double Hydroxide Nanoparticles by Coating/Detaching pH-Triggered Charge-Convertible Polymers.

ACS Omega 2021 Feb 27;6(5):3822-3830. Epub 2021 Jan 27.

Department of Pathology, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province 250014, People's Republic of China.

Layered double hydroxide (LDH) nanoparticles are extensively explored as multifunctional nanocarriers due to their versatility in both the host layer and the interlayer anion. In this study, we report modification of positively charged Cu-containing LDH nanoparticles with a pH-responsive charge-changeable polymer to improve the particle colloidal stability in blood circulation, reduce the nonspecific uptake by normal cells in organs, and subsequently facilitate tumor accumulation and uptake by tumor cells in the acidic tumor microenvironment. experimental results demonstrate that this promising charge-convertible polymer-LDH nanocarrier well reduces the capture by macrophages in the physiologic medium (pH 7.4) but facilitates the uptake by tumor cells due to detaching of the coated polymer layer in the weakly acidic condition (pH 6.8). Cu-containing LDH nanoparticles also show pH-responsive magnetic resonance imaging (MRI) contrast capacity (i.e., relaxivity). MRI further confirms effective tumor accumulation of the charge-convertible nanohybrids, with ∼4.8% of the injected dose accumulated at 24 h postintravenous injection, proving the potential as a versatile delivery nanocarrier to enhance the antitumor treatment.
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http://dx.doi.org/10.1021/acsomega.0c05520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876861PMC
February 2021

OsUEV1B, an Ubc enzyme variant protein, is required for phosphate homeostasis in rice.

Plant J 2021 May 6;106(3):706-719. Epub 2021 Apr 6.

Center for Plant Water-use and Nutrition Regulation and College of Life Sciences, Joint International Research Laboratory of Water and Nutrient in Crop, Fujian Agriculture and Forestry University, Fuzhou, China.

Phosphorus is a crucial macronutrient for plant growth and development. The mechanisms for maintaining inorganic phosphate (Pi) homeostasis in rice are not well understood. The ubiquitin-conjugating enzyme variant protein OsUEV1B was previously found to interact with OsUbc13 and mediate lysine63-linked polyubiquitination. In the present study, we found OsUEV1B was specifically inhibited by Pi deficiency, and was localized in the nucleus and cytoplasm. Both osuev1b mutant and OsUEV1B-RNA interference (RNAi) lines displayed serious symptoms of toxicity due to Pi overaccumulation. Some Pi starvation inducible and phosphate transporter genes were upregulated in osuev1b mutant and OsUEV1B-RNAi plants in association with enhanced Pi acquisition, and representative Pi starvation responses, including stimulation of acid phosphatase activity and root hair growth, were also activated in the presence of sufficient Pi. A yeast two-hybrid screen revealed an interaction between OsUEV1B and OsVDAC1, which was confirmed by bimolecular fluorescence complementation and firefly split-luciferase complementation assays. OsVDAC1 encoded a voltage-dependent anion channel protein localized in the mitochondria, and OsUbc13 was shown to interact with OsVDAC1 via yeast two-hybrid and bimolecular fluorescence complementation assays. Under sufficient Pi conditions, similar to osuev1b, a mutation in OsVDAC1 resulted in significantly greater Pi concentrations in the roots and second leaves, improved acid phosphatase activity, and enhanced expression of the Pi starvation inducible and phosphate transporter genes compared with wild-type DongJin, whereas overexpression of OsVDAC1 had the opposite effects. OsUEV1B or OsVDAC1 knockout reduced the mitochondrial membrane potential and adenosine triphosphate levels. Moreover, overexpression of OsVDAC1 in osuev1b partially restored its high Pi concentration to a level between those of osuev1b and DongJin. Our results indicate that OsUEV1B is required for rice phosphate homeostasis.
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http://dx.doi.org/10.1111/tpj.15193DOI Listing
May 2021

Synergistic Cancer Photochemotherapy via Layered Double Hydroxide-Based Trimodal Nanomedicine at Very Low Therapeutic Doses.

ACS Appl Mater Interfaces 2021 Feb 5;13(6):7115-7126. Epub 2021 Feb 5.

Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, St Lucia, QLD 4072, Australia.

The success of cancer therapy is always accompanied by severe side effects due to the high amount of toxic antitumor drugs that off-target normal organs/tissues. Herein, we report the development of a trifunctional layered double hydroxide (LDH) nanosystem for combined photochemotherapy of skin cancer at very low therapeutic doses. This nanosystem (ICG/[email protected]) is composed of acid-responsive bovine serum albumin-doxorubicin prodrug (BSA-DOX) and indocyanine green (ICG)-intercalated Cu-doped LDH nanoparticle. ICG/[email protected] is able to release DOX in an acid-triggered manner, efficiently and simultaneously generates heating and reactive oxygen species (ROS) upon 808 nm laser irradiation, and synergistically induces apoptosis of skin cancer cells. In vivo therapeutic evaluations demonstrate that ICG/[email protected] nearly eradicated the tumor tissues upon one-course treatment using very low doses of therapeutic agents (0.175 mg/kg DOX, 0.5 mg/kg Cu, and 0.25 mg/kg ICG) upon very mild 808 nm laser irradiation (0.3 W/cm for 2 min). This work thus provides a novel strategy to design anticancer nanomedicine for efficient combination cancer treatment with minimal side effects in clinical applications.
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http://dx.doi.org/10.1021/acsami.0c23143DOI Listing
February 2021

Oral application of Chinese herbal medicine for allergic rhinitis: A systematic review and meta-analysis of randomized controlled trials.

Phytother Res 2021 Jun 3;35(6):3113-3129. Epub 2021 Feb 3.

School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria, Australia.

Chinese herbal medicine (CHM) has long been used for allergic rhinitis (AR). This systematic review aimed to investigate the clinical effects and safety of oral CHM for AR by comparing it to Western medications (WM). Nineteen databases were searched up to May 27, 2020. Randomized controlled trials (RCTs) assessing the effects of CHM on the primary or secondary outcomes comparing to WM, in any age of the patients, were included. The pooled results were expressed as mean difference, standardized mean difference, or odds ratio with 95% confidence intervals. Eighteen RCTs were included and 17 of them were evaluated in the meta-analysis. CHM may improve total nasal symptom scores, individual symptom scores (rhinorrhea, nasal congestion, sneezing, and nasal itching), quality of life, and recurrence rate, compared to antihistamines (loratadine and chlorpheniramine). Only mild and transient adverse events of CHM were reported. However, there were no significant differences in some subgroup analyses in total nasal symptom scores, rhinorrhea, nasal obstruction, sneezing, nasal itching, and SF-36. Due to the small number of included studies, poor quality of trial design, and substantial heterogeneities, the potential of CHM for AR should be validated in large, multicenter, and well-designed RCTs in the future.
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http://dx.doi.org/10.1002/ptr.7037DOI Listing
June 2021

Addition of Aβ to Total Cerebral Small Vessel Disease Score Improves the Prediction for Cognitive Impairment in Cerebral Small Vessel Disease Patients.

Neuropsychiatr Dis Treat 2021 25;17:195-201. Epub 2021 Jan 25.

Department of Neurology, Tianjin Medical University General Hospital, Tianjin 300052, People's Republic of China.

Purpose: To investigate the associations between concentrations of Aβ and Aβ and vascular cognitive impairment (VCI) in cerebral small vessel disease (CSVD) patients and evaluate the value of combination of levels of Aβ or Aβ and the total CSVD score in predicting VCI.

Patients And Methods: A total of 199 CSVD patients were divided into VCI group and non-VCI group according to the criteria of VCI. Demographic data, MRI markers of CSVD, blood pressure, vascular risk factors, laboratory markers, and serum Aβ and Aβ concentration were collected. Univariate analysis was performed with the Student's -test, Mann-Whitney -test or Chi-square test. Variables with <0.10 in univariate analysis were then included in multivariate analysis that used a backward stepwise logistic regression model. The predictive values were assessed with receiver operating characteristic (ROC) curve.

Results: VCI was determined in 112 CSVD patients (56.3%). Hyperlipidemia (OR: 1.618, 95% CI: 1.265-3.049), the total CSVD score (OR: 1.414, 95% CI: 1.213-2.278) and serum Aβ concentration (OR: 1.401, 95% CI: 1.212-1.946) were independent risk factors for VCI in CSVD patients with adjustment for age, education years, diabetes and fasting blood-glucose (FBG). The area under curves (AUCs) were 0.640 (SE: 0.040, 95% CI: 0.563-0.718), 0.733 (SE: 0.035, 95% CI: 0.664-0.802) and 0.827 (SE: 0.030, 95% CI: 0.768-0.887), respectively, for the total CSVD score, serum Aβ concentration and their combination applied in predicting VCI in CSVD patients. test demonstrated that the AUC of combination prediction was significantly higher than individual prediction (0.827 vs 0.640, =3.740, <0.001; 0.827 vs 0.733, =2.039, =0.021).

Conclusion: Combination of Aβ and total CSVD score could significantly elevate the predictive value of cognitive impairment in CSVD patients.
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http://dx.doi.org/10.2147/NDT.S289357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846822PMC
January 2021

HSP60 Regulates Monosodium Urate Crystal-Induced Inflammation by Activating the TLR4-NF-B-MyD88 Signaling Pathway and Disrupting Mitochondrial Function.

Oxid Med Cell Longev 2020 31;2020:8706898. Epub 2020 Dec 31.

Institute of Rheumatology and Immunology, The Affiliated Hospital of North Sichuan Medical College, 63# Wenhua Road, Nanchong, 637000 Sichuan, Nanchong, China.

Acute gout is an inflammatory response induced by monosodium urate (MSU) crystals. HSP60 is a highly conserved stress protein that acts as a cellular "danger" signal for immune reactions. In this study, we aimed to investigate the role and molecular mechanism of HSP60 in gout. HSP60 expression was detected in peripheral blood mononuclear cells (PBMCs) and plasma of gout patients. The effect and molecular mechanism of HSP60 in gout were studied in MSU crystals treatment macrophages and C57BL/6 mice. JC-1 probe and MitoSOX Red were used to measure the mitochondrial membrane potential (MMP) and mitochondrial reactive oxygen species (mtROS). HSP60 expression was significantly upregulated in the PBMCs and sera of patients with acute gout (AG) compared to those with intercritical gout (IG) or healthy controls (HCs). MSU crystals induced the expression and secretion of HSP60 in the macrophages. HSP60 knockdown or overexpression affects TLR4 and MyD88 expression, IB degradation, and the nuclear localization of NF-B in MSU crystal-stimulated inflammation. Further, HSP60 facilitates MMP collapse and mtROS production and activates the NLRP3 inflammasome in MSU crystal-stimulated macrophages. In MSU crystal-induced arthritis mouse models pretreated with HSP60 vivo-morpholino, paw swelling, myeloperoxidase (MPO) activity, and inflammatory cell infiltration significantly decreased. Our study reveals that MSU crystal stimulates the expression of HSP60, which accelerates the TLR4-MyD88-NF-B signaling pathway and exacerbates mitochondrial dysfunction.
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http://dx.doi.org/10.1155/2020/8706898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791970PMC
December 2020

Influencing factors and drug application of iontophoresis in transdermal drug delivery: an overview of recent progress.

Drug Deliv Transl Res 2021 Jan 23. Epub 2021 Jan 23.

Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Jiangsu Province, Nanjing, 211198, China.

Transdermal drug delivery is limited by the stratum corneum of skin, which blocks most molecules, and thus, only few molecules with specific physicochemical properties (molecular weight < 500 Da, adequate lipophilicity, and low melting point) are able to penetrate the skin. Recently, various technologies have been developed to overcome the strong barrier properties of stratum corneum. Iontophoresis technology, which uses a small current to improve drug permeation through skin, is one of the effective ways to circumvent the stratum corneum. This approach not only provides a more efficient, noninvasive, and patient-friendly method of drug delivery but also widens the scope of drugs for transdermal delivery. In this review, the mechanisms underlying iontophoresis and affecting factors are outlined. The focus will be on the latest advancements in iontophoretic transdermal drug delivery and application of iontophoresis with other enhancing technologies. The challenges of this technology for drug administration have also been highlighted, and some iontophoretic systems approved for clinical use are described.
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http://dx.doi.org/10.1007/s13346-021-00898-6DOI Listing
January 2021

A Ruthenium(II) complex-based probe for colorimetric and luminescent detection and imaging of hydrogen sulfide in living cells and organisms.

Anal Chim Acta 2021 Feb 11;1145:114-123. Epub 2020 Nov 11.

Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, Queensland, 4072, Australia. Electronic address:

The development of reliable bioanalytical probes for sensitive and specific detection of hydrogen sulfide (HS) plays important role for better understanding the roles of this biomolecule in living cells and organisms. Taking advantages of unique photophysical properties of ruthenium(II) (Ru(II)) complex, this work presents the development of a responsive Ru(II) complex probe, Ru-PNBD, for colorimetric and luminescent analysis of HS in living cells and organisms. In aqueous solution, Ru-PNBD is yellow color and non-luminescent because of the photoinduced electron transfer (PET) process from Ru(II) complex luminophore to NBD moiety. The HS-triggered specific nucleophilic substitution reaction with Ru-PNBD cleaves the NBD moiety to form pink NBD-SH and highly luminescent Ru-PH. The color of the solution thus changes from yellow to pink for colorimetric analysis and the emission intensity is about 65-fold increased for luminescent analysis. Ru-PNBD has high sensitivity and selectivity for HS detection, low cytotoxicity and good permeability to cell membrane, which allow the application of this probe for HS imaging in living cells, Daphnia magna, and larval zebrafish. Collectively, this work provides a useful tool for HS analysis and expands the scope of transition metal complex probes.
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http://dx.doi.org/10.1016/j.aca.2020.11.009DOI Listing
February 2021