Publications by authors named "Haiyan Zhang"

651 Publications

Pseudolaric acid B ameliorates synovial inflammation and vessel formation by stabilizing PPARγ to inhibit NF-κB signalling pathway.

J Cell Mol Med 2021 Jun 11. Epub 2021 Jun 11.

Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.

Synovial macrophage polarization and inflammation are essential for osteoarthritis (OA) development, yet the molecular mechanisms and regulation responsible for the pathogenesis are still poorly understood. Here, we report that pseudolaric acid B (PAB) attenuated articular cartilage degeneration and synovitis during OA. PAB, a diterpene acid, specifically inhibited NF-κB signalling and reduced the production of pro-inflammatory cytokines, which further decreased M1 polarization and vessel formation. We further provide in vivo and in vitro evidences that PAB suppressed NF-κB signalling by stabilizing PPARγ. Using PPARγ antagonist could abolish anti-inflammatory effect of PAB and rescue the activation of NF-κB signalling during OA. Our findings identify a previously unrecognized role of PAB in the regulation of OA and provide mechanisms by which PAB regulates NF-κB signalling through PPARγ, which further suggest targeting synovial inflammation or inhibiting vessel formation at early stage could be an effective preventive strategy for OA.
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http://dx.doi.org/10.1111/jcmm.16670DOI Listing
June 2021

Preparation and characterization of paclitaxel palmitate albumin nanoparticles with high loading efficacy: an in vitro and in vivo anti-tumor study in mouse models.

Drug Deliv 2021 Dec;28(1):1067-1079

Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China.

Background: Combination of the prodrug technique with an albumin nano drug-loaded system is a novel promising approach for cancer treatment. However, the long-lasting and far-reaching challenge for the treatment of cancers lies in how to construct the albumin nanometer drug delivery system with lead compounds and their derivatives.

Methods: In this study, we reported the preparation of injectable albumin nanoparticles (NPs) with a high and quantitative drug loading system based on the Nab technology of paclitaxel palmitate (PTX-PA).

Results: Our experimental study on drug tissue distribution in vivo demonstrated that the paclitaxel palmitate albumin nanoparticles (Nab-PTX-PA) remained in the tumor for a longer time post-injection. Compared with saline and paclitaxel albumin nanoparticles (Abraxane), intravenous injection of Nab-PTX-PA not only reduced the toxicity of the drug in normal organs, and increased the body weight of the animals but maintained sustained release of paclitaxel (PTX) in the tumor, thereby displaying an excellent antitumor activity. Blood routine analysis showed that Nab-PTX-PA had fewer adverse effects or less toxicity to the normal organs, and it inhibited tumor cell proliferation more effectively as compared with commercial paclitaxel albumin nanoparticles.

Conclusions: This carrier strategy for small molecule drugs is based on naturally evolved interactions between long-chain fatty acids (LCFAs) and Human Serum Albumin (HSA), demonstrated here for PTX. Nab-PTX-PA shows higher antitumor efficacy in vivo in breast cancer models. On the whole, this novel injectable Nab-PTX-PA has great potential as an effective drug delivery system in the treatment of breast cancer.
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http://dx.doi.org/10.1080/10717544.2021.1921078DOI Listing
December 2021

A phase I study of the safety and activity of K-001 in patients with advanced pancreatic ductal adenocarcinoma.

BMC Cancer 2021 Jun 7;21(1):672. Epub 2021 Jun 7.

Department of Medical Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease that lack of effective therapeutic drugs. K-001 is an oral antitumor drug made from active ingredients of marine microorganisms. The current study aimed to evaluate safety and antitumor activity of K-001 in patients with advanced PDAC.

Methods: In this phase I, open-label trial, patients with advanced PDAC were recruited to a dose-escalation study in a standard 3 + 3 design. K-001 was administered twice daily in four-week cycles, and dose escalation from 1350 mg to 2160 mg was evaluated twice daily. Physical examination and laboratory tests were done at screening and then weekly. The safety, dose-limiting toxicity (DLT), and maximum tolerated dose (MTD) of K-001 were assessed while tumor response was estimated by Response Evaluation Criteria in Solid Tumor (RECIST).

Results: Eighteen patients with advanced PDAC were screened, and twelve eligible patients were analyzed in the study. No DLT was observed. Totally, 47 adverse events (AEs) presented, and 14 drug-related AEs were reported in 7 patients, including 8 grade 1 events (57.1%) and 6 grade 2 events (42.9%). There was no grade 3 or 4 drug-related AE. In these 14 drug-related AEs, the most frequent ones were dyspepsia (21.4%), followed by flatulence, constipation, and hemorrhoid bleeding (above 10% of each). Among all 12 patients, 10 patients (83.3%) maintained stable disease (SD), and 2 patients (16.7%) had progressive disease (PD). The objective response rate (ORR) was 0% and the disease control rate (DCR) was 83.3%.

Conclusions: K-001 manifests satisfactory safety and tolerability, as well as meaningful antitumor activity in advanced PDAC patients. Further evaluation of K-001 in phase II/III appears warranted.

Trial Registration: NCT02720666 . Registered 28 Match 2016 - Retrospectively registered.
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http://dx.doi.org/10.1186/s12885-021-08375-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183060PMC
June 2021

Genomes of Anguillid Herpesvirus 1 Strains Reveal Evolutionary Disparities and Low Genetic Diversity in the Genus .

Microorganisms 2021 May 5;9(5). Epub 2021 May 5.

Immunology-Vaccinology, Department of Infectious and Parasitic Diseases, Fundamental and Applied Research for Animals & Health (FARAH), Faculty of Veterinary Medicine, University of Liège, B-4000 Liège, Belgium.

Anguillid herpesvirus 1 (AngHV-1) is a pathogen of eels and a member of the genus in the family . We have compared the biological and genomic features of different AngHV-1 strains, focusing on their growth kinetics in vitro and genetic content, diversity, and recombination. Comparisons based on three core genes conserved among alloherpesviruses revealed that AngHV-1 exhibits a slower rate of change and less positive selection than other cypriniviruses. We propose that this may be linked to major differences in host species and corresponding epidemiological circumstances. Efforts to derive evolutionary rate estimates for cypriniviruses under various theoretical models were ultimately unrewarding. We highlight the potential value of future collaborative efforts towards generating short-term evolutionary rate estimates based on known sequence sampling dates. Finally, we revealed that there is significantly less genetic diversity in core gene sequences within cyprinivirus species clades compared to species in the family . This suggests that cyprinivirus species may have undergone much more vigorous purifying selection post species clade divergence. We discuss whether this may be linked to biological and anthropogenic factors or to sampling bias, and we propose that the comparison of short-term evolutionary rates between species may provide further insights into these differences.
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http://dx.doi.org/10.3390/microorganisms9050998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148134PMC
May 2021

Application of iron/barium ferrite/carbon-coated iron nanocrystal composites in transcatheter arterial chemoembolization of hepatocellular carcinoma.

J Colloid Interface Sci 2021 May 21;601:30-41. Epub 2021 May 21.

State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, Guangdong 510060, China; Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China. Electronic address:

Transcatheter arterial chemoembolization (TACE) has been widely used in clinical practice as a first-line treatment for unresectable hepatocellular carcinoma (HCC). However, the current therapeuticeffect of TACE is far from satisfactory and thus requires further improvement. TACE combined with multifunctional magnetic particles may be a promising approach for the treatment of HCC. In this study, we designed a new magnetic drug carrier system consisting of micron-sized iron powder, barium ferrite (BaFeO), and carbon-coated iron nanocrystals (CCINs). CCINs possess properties, such as high drug loading and sustained release. BaFeO could attract both CCINs and iron powder to form larger clusters after magnetization. Altogether, the triple therapeutic effects of chemotherapeutic enhancement, embolization, and thermal ablation could be realized herein. Further experiments indicate that the system has a high drug-loading capacity, good controlled-release effect, and no significant cytotoxicity. Under the action of a medium-frequency magnetic induction device, the magnetic induction temperature could reach 43 °C in one min while the maximum temperature of 70.8 °C could be reached in 2.5 h. Overall, this new carrier system displayed excellent antitumor effects in a mouse model. Our findings demonstrate the great application prospects of this system in TACE for HCC.
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http://dx.doi.org/10.1016/j.jcis.2021.05.102DOI Listing
May 2021

Seed biostimulant Bacillus sp. MGW9 improves the salt tolerance of maize during seed germination.

AMB Express 2021 May 25;11(1):74. Epub 2021 May 25.

Dryland Technology Key Laboratory of Shandong Province, Qingdao Agricultural University, Qingdao, 266109, China.

Crop performance is seriously affected by high salt concentrations in soils. To develop improved seed pre-sowing treatment technologies, it is crucial to improve the salt tolerance of seed germination. Here, we isolated and identified the strain Bacillus sp. MGW9 and developed the seed biostimulant MGW9. The effects of seed biopriming with the seed biostimulant MGW9 in maize (Zea mays L.) under saline conditions were studied. The results show that the strain Bacillus sp. MGW9 has characteristics such as salt tolerance, nitrogen fixation, phosphorus dissolution, and indole-3-acetic acid production. Seed biopriming with the seed biostimulant MGW9 enhanced the performance of maize during seed germination under salinity stress, improving the germination energy, germination percentage, shoot/seedling length, primary root length, shoot/seedling fresh weight, shoot/seedling dry weight, root fresh weight and root dry weight. Seed biostimulant MGW9 biopriming also alleviated the salinity damage to maize by improving the relative water content, chlorophyll content, proline content, soluble sugar content, root activity, and activities of superoxide dismutase, catalase, peroxidase and ascorbate peroxidase, while decreasing the malondialdehyde content. In particular, the field seedling emergence of maize seeds in saline-alkali soil can be improved by biopriming with the seed biostimulant MGW9. Therefore, maize seed biopriming with the seed biostimulant MGW9 could be an effective approach to overcoming the inhibitory effects of salinity stress and promoting seed germination and seedling growth.
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http://dx.doi.org/10.1186/s13568-021-01237-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149540PMC
May 2021

MFG-E8 regulated by miR-99b-5p protects against osteoarthritis by targeting chondrocyte senescence and macrophage reprogramming via the NF-κB pathway.

Cell Death Dis 2021 May 25;12(6):533. Epub 2021 May 25.

Department of Joint Surgery, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.

Milk fat globule-epidermal growth factor (EGF) factor 8 (MFG-E8), as a necessary bridging molecule between apoptotic cells and phagocytic cells, has been widely studied in various organs and diseases, while the effect of MFG-E8 in osteoarthritis (OA) remains unclear. Here, we identified MFG-E8 as a key factor mediating chondrocyte senescence and macrophage polarization and revealed its role in the pathology of OA. We found that MFG-E8 expression was downregulated both locally and systemically as OA advanced in patients with OA and in mice after destabilization of the medial meniscus surgery (DMM) to induce OA. MFG-E8 loss caused striking progressive articular cartilage damage, synovial hyperplasia, and massive osteophyte formation in OA mice, which was relieved by intra-articular administration of recombinant mouse MFG-E8 (rmMFG-E8). Moreover, MFG-E8 restored chondrocyte homeostasis, deferred chondrocyte senescence and reprogrammed macrophages to the M2 subtype to alleviate OA. Further studies showed that MFG-E8 was inhibited by miR-99b-5p, expression of which was significantly upregulated in OA cartilage, leading to exacerbation of experimental OA partially through activation of NF-κB signaling in chondrocytes. Our findings established an essential role of MFG-E8 in chondrocyte senescence and macrophage reprogramming during OA, and identified intra-articular injection of MFG-E8 as a potential therapeutic target for OA prevention and treatment.
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http://dx.doi.org/10.1038/s41419-021-03800-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144578PMC
May 2021

Discovery of Novel Tacrine-Pyrimidone Hybrids as Potent Dual AChE/GSK-3 Inhibitors for the Treatment of Alzheimer's Disease.

J Med Chem 2021 06 23;64(11):7483-7506. Epub 2021 May 23.

State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.

Based on a multitarget strategy, a series of novel tacrine-pyrimidone hybrids were identified for the potential treatment of Alzheimer's disease (AD). Biological evaluation results demonstrated that these hybrids exhibited significant inhibitory activities toward acetylcholinesterase (AChE) and glycogen synthase kinase 3 (GSK-3). The optimal compound possessed excellent dual AChE/GSK-3 inhibition both in terms of potency and equilibrium (AChE: IC = 51.1 nM; GSK-3β: IC = 89.3 nM) and displayed significant amelioration on cognitive deficits in scopolamine-induced amnesia mice and efficient reduction against phosphorylation of tau protein on Ser-199 and Ser-396 sites in glyceraldehyde (GA)-stimulated differentiated SH-SY5Y cells. Furthermore, compound exhibited eligible pharmacokinetic properties, good kinase selectivity, and moderate neuroprotection against GA-induced reduction in cell viability and neurite damage in SH-SY5Y-derived neurons. The multifunctional profiles of compound suggest that it deserves further investigation as a promising lead for the prospective treatment of AD.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00160DOI Listing
June 2021

Direct Modification of Multiple Gene Homoeologs in Brassica oleracea and Brassica napus Using Doubled Haploid Inducer-Mediated Genome Editing System.

Plant Biotechnol J 2021 May 19. Epub 2021 May 19.

Oil Crops Research Institute of Chinese Academy of Agricultural Sciences, Key Laboratory of Biology and Genetic Improvement of Oil Crops, Ministry of Agriculture, No.2 Xudong 2nd Road, Wuhan, 430062, People's Republic of China.

The diploid Brassica oleracea and allopolyploidy Brassica napus are predominant members of commonly consumed vegetables and plant oil, respectively. B. oleracea vegetables mainly include Broccoli, Cauliflower, Cabbage, Brussels sprouts and Kohlrabi. The complex genome structure and gene function redundancy are the main obstacles for gene stacking through traditional cross breeding approach. To solve this problem, high-efficiency CRISPR/Cas9 genome editing technologies have been established (Lawrenson et al., 2015; Li et al., 2018). However, an open question is that most of these established approaches employed Agrobacterium-mediated T-DNA transformation to deliver CRISRP/Cas9 components into plant cells, which would unavoidably introduce exogenous large DNA fragments. Moreover, Agrobacterium-based strategy deeply relies on transformation efficiency of the recipient genotype, which extremely restricts rapid application of CRISRP/Cas9 in the majority of elite commercial verities.
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http://dx.doi.org/10.1111/pbi.13632DOI Listing
May 2021

ALA-PDT successfully treated Majocchi's granuloma by directly killing Trichophyton tonsurans and recruiting T lymphocytes.

Photodiagnosis Photodyn Ther 2021 May 15;35:102328. Epub 2021 May 15.

Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Baode Road 1278, Shanghai, 200443, China. Electronic address:

Background: Majocchi's granuloma (MG) is a deep persistent suppurative granulomatous perifolliculitis which might be caused by Trichophyton tonsurans (T. tonsurans). Conventional treatment for MG is oral administration of systematic antifungal drugs, associated with a low cure rate and a high relapse rate. ALA-PDT is a new approach for fungal infection.

Methods: A case of refractory MG was treated by 3 times of ALA-PDT. At the same time, T. tonsurans strains isolated from the lesions of the patient were used for an in vitro inhibition experiment and an in vivo experiment in guinea pig model to furtherly verify the effectiveness and investigate the mechanism of ALA-PDT for T. tonsurans.

Results: After 3 times of ALA-PDT, the lesions of MG were eliminated. And the mycological and pathological examination showed a disappearance of fungi in follicles. In vitro and in vivo experiment both demonstrated that ALA-PDT could obviously inhibit the growth of T. tonsurans partly by directly destroying the structure of fungal cells and recruiting CD4 + T cells.

Conclusion: ALA-PDT is a potentially effective noninvasive method for the treatment of MG with mechanisms of direct killing and with CD4 T cell-mediated immune response.
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http://dx.doi.org/10.1016/j.pdpdt.2021.102328DOI Listing
May 2021

Fargesin ameliorates osteoarthritis via macrophage reprogramming by downregulating MAPK and NF-κB pathways.

Arthritis Res Ther 2021 05 14;23(1):142. Epub 2021 May 14.

Department of Joint Surgery, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.

Background: To investigate the role and regulatory mechanisms of fargesin, one of the main components of Magnolia fargesii, in macrophage reprogramming and crosstalk across cartilage and synovium during osteoarthritis (OA) development.

Methods: Ten-week-old male C57BL/6 mice were randomized and assigned to vehicle, collagenase-induced OA (CIOA), or CIOA with intra-articular fargesin treatment groups. Articular cartilage degeneration was evaluated using the Osteoarthritis Research Society International (OARSI) score. Immunostaining and western blot analyses were conducted to detect relative protein. Raw264.7 cells were treated with LPS or IL-4 to investigate the role of polarized macrophages. ADTC5 cells were treated with IL-1β and conditioned medium was collected to investigate the crosstalk between chondrocytes and macrophages.

Results: Fargesin attenuated articular cartilage degeneration and synovitis, resulting in substantially lower Osteoarthritis Research Society International (OARSI) and synovitis scores. In particular, significantly increased M2 polarization and decreased M1 polarization in synovial macrophages were found in fargesin-treated CIOA mice compared to controls. This was accompanied by downregulation of IL-6 and IL-1β and upregulation of IL-10 in serum. Conditioned medium (CM) from M1 macrophages treated with fargesin reduced the expression of matrix metalloproteinase-13, RUNX2, and type X collagen and increased Col2a1 and SOX9 in OA chondrocytes, but fargesin alone did not affect chondrocyte catabolic processes. Moreover, fargesin exerted protective effects by suppressing p38/ERK MAPK and p65/NF-κB signaling.

Conclusions: This study showed that fargesin switched the polarized phenotypes of macrophages from M1 to M2 subtypes and prevented cartilage degeneration partially by downregulating p38/ERK MAPK and p65/NF-κB signaling. Targeting macrophage reprogramming or blocking the crosstalk between macrophages and chondrocytes in early OA may be an effective preventive strategy.
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http://dx.doi.org/10.1186/s13075-021-02512-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120707PMC
May 2021

A Phenothiazine-HPQ Based Fluorescent Probe with a Large Stokes Shift for Sensing Biothiols in Living Systems.

Molecules 2021 Apr 17;26(8). Epub 2021 Apr 17.

College of Pharmacy, Qiqihar Medical University, Qiqihar 161006, China.

Due to the redox properties closely related to numerous physiological and pathological processes, biothiols, including cysteine (Cys), homocysteine (Hcy) and glutathione (GSH), have received considerable attention in biological science. On account of the important physiological roles of these biothiols, it is of profound significance to develop sensitive and selective detection of biothiols to understand their biological profiles. In this work, we reported an efficient fluorescent probe, , for detecting biothiols in vitro and vivo, based on the phenothiazine-HPQ skeleton, with DNBS (2,4-dinitrobenzenesulfonate) as the response unit. Probe exhibited brilliant sensing performances toward thiols, including a large Stokes shift (138 nm), excellent sensitivity (for GSH, LOD = 18.3 nM), remarkable fluorescence enhancement (163-fold), low cytotoxicity, rapid response (8 min), and extraordinary selectivity. Finally, the probe illustrated herein was capable of responding and visualizing biothiols in MCF-7 cells and zebrafish.
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http://dx.doi.org/10.3390/molecules26082337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072808PMC
April 2021

Associations of frailty, loneliness and the quality of life of empty nesters: A cross-sectional study in rural areas.

Int J Nurs Pract 2021 Apr 25:e12947. Epub 2021 Apr 25.

School of Nursing, Jilin University, Changchun, China.

Aims: To explore loneliness, in association with frailty, in explaining the quality of life (QOL) of empty-nest older adults in rural China.

Design: A cross-sectional questionnaire survey was conducted.

Methods: Data collection was performed from June to August 2017 in Changchun, the capital city of Jilin province, which consists of seven districts and three counties. In total, 304 older adults aged 60 years and above participated. The characteristics of older adults were evaluated in terms of frailty status, loneliness and the QOL. One-way and two-way analyses of covariance and the area under the receiver operating characteristic curves were used to explore the relationships of frailty, loneliness and the QOL.

Results: The one-way ANCOVA showed a significant difference among robust, prefrail and frail participants for loneliness. Moreover, an interaction effect of frailty with loneliness in determining the QOL was found. The receiver operating characteristic curves showed that loneliness and QOL could distinguish frail older adults, and the best cutoffs were 34.5 and 67.4, respectively.

Conclusion: This study demonstrates a close relationship between frailty and loneliness, suggesting the need to simultaneously consider the two with regard to the QOL of empty-nest older adults in rural China.

Summary Statement: What is already known about this topic? There were no studies examining the associations of frailty and loneliness with QOL or the cut-point of the loneliness and QOL scores to reflect frailty. Few studies have revealed an association between loneliness and frailty. These studies focus mainly on older adults living in the community, and none consider the relationship between mental status and the frailty of empty nesters. What this paper adds? This study determined that frailty, loneliness and the QOL had a close relationship in empty nesters. There was a significant interaction among frailty, loneliness and the quality of life. Loneliness and the QOL could distinguish frail older adults, and the best cutoffs were 34.5 and 67.4, respectively. The implications of this paper? This study can enable governments and communities to pay attention to the psychological status of empty-nest individuals while paying attention to their psychological problems, such as loneliness, to help them improve their quality of life.
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http://dx.doi.org/10.1111/ijn.12947DOI Listing
April 2021

Generation of an induced pluripotent stem cell line SDQLCHi026-A from a hereditary tyrosinemia type I patient carrying compound heterozygote mutations in FAH gene.

Stem Cell Res 2021 May 9;53:102331. Epub 2021 Apr 9.

Pediatric Research Institute, Qilu Children's Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250022, China. Electronic address:

Here we describe the generation of induced pluripotent stem cells (iPSCs) from a patient diagnosed as hereditary tyrosinemia type I (HT1) caused by FAH gene mutation. Induced pluripotent stem cells (iPSCs) were developed using non-integrating episomal vectors containing OCT4, SOX2, KLF4, BCL-XL and MYC. The established iPSC line (SDQLCHi026-A) displayed pluripotent cell morphology, high expression levels of pluripotency markers, differentiation potential in vitro, normal karyotype, and remaining the original FAH gene mutation.
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http://dx.doi.org/10.1016/j.scr.2021.102331DOI Listing
May 2021

Blocking polymerization of CTFs induces plentiful structural terminations for synchronous removal of organics and Cr(VI).

Chem Commun (Camb) 2021 May;57(40):4946-4949

Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou, Zhejiang 310032, P. R. China.

Herein, an ultramild block polymerization strategy was employed to precisely control the exposure of structural terminations in the skeleton of covalent triazine-based frameworks (CTFs). The generated structural terminations with cyano (-CN) and hydroxy (-OH) groups (STCHs) could serve as not only the optimal adsorption sites for enriching targets, but also π-conjugated electron donor-acceptor dyads to accelerate the charge transfer. With spatial separation of charge localization sites, STCH-CTF exhibited a photoactivity of 2.5-4 times higher than that of pristine CTFs in the simultaneous oxidation of bisphenol A (BPA) and the reduction of hexavalent chromium (Cr(vi)).
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http://dx.doi.org/10.1039/d1cc00780gDOI Listing
May 2021

Voluntary wheel running complements microdystrophin gene therapy to improve muscle function in mdx mice.

Mol Ther Methods Clin Dev 2021 Jun 3;21:144-160. Epub 2021 Mar 3.

Department of Human Nutrition, Foods, and Exercise and Metabolism Core, Virginia Tech, Blacksburg, VA 24060, USA.

We tested the hypothesis that voluntary wheel running would complement microdystrophin gene therapy to improve muscle function in young mdx mice, a model of Duchenne muscular dystrophy. mdx mice injected with a single dose of AAV9-CK8-microdystrophin or vehicle at age 7 weeks were assigned to three groups: mdxRGT (run, gene therapy), mdxGT (no run, gene therapy), or mdx (no run, no gene therapy). Wild-type (WT) mice were assigned to WTR (run) and WT (no run) groups. WTR and mdxRGT performed voluntary wheel running for 21 weeks; remaining groups were cage active. Robust expression of microdystrophin occurred in heart and limb muscles of treated mice. mdxRGT versus mdxGT mice showed increased microdystrophin in quadriceps but decreased levels in diaphragm. mdx final treadmill fatigue time was depressed compared to all groups, improved in mdxGT, and highest in mdxRGT. Both weekly running distance (km) and final treadmill fatigue time for mdxRGT and WTR were similar. Remarkably, mdxRGT diaphragm power was only rescued to 60% of WT, suggesting a negative impact of running. However, potential changes in fiber type distribution in mdxRGT diaphragms could indicate an adaptation to trade power for endurance. Post-treatment maximal plantar flexor torque relative to baseline values was greater for mdxGT and mdxRGT versus all other groups. Mitochondrial respiration rates from red quadriceps fibers were significantly improved in mdxGT animals, but the greatest bioenergetic benefit was observed in the mdxRGT group. Additional assessments revealed partial to full functional restoration in mdxGT and mdxRGT muscles relative to WT. These data demonstrate that voluntary wheel running combined with microdystrophin gene therapy in young mdx mice improved whole-body performance, affected muscle function differentially, mitigated energetic deficits, but also revealed some detrimental effects of exercise. With microdystrophin gene therapy currently in clinical trials, these data may help us understand the potential impact of exercise in treated patients.
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http://dx.doi.org/10.1016/j.omtm.2021.02.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020351PMC
June 2021

The fate of flavonoids after oral administration: a comprehensive overview of its bioavailability.

Crit Rev Food Sci Nutr 2021 Apr 13:1-18. Epub 2021 Apr 13.

Jiangxi University of Traditional Chinese Medicine, Nanchang, PR China.

Despite advancements in synthetic chemistry, nature remains the primary source of drug discovery, and this never-ending task of finding novel and active drug molecules will continue. Flavonoids have been shown to possess highly significant therapeutic activities such as anti-inflammatory, anti-oxidant, anti-viral, anti-diabetic, anti-cancer, anti-aging, neuroprotective, and cardioprotective, etc., However, it has been found that orally administered flavonoids have a critical absorption disorder and, therefore, have low bioavailability and show fluctuating pharmacokinetic and pharmacodynamic responses. A detailed investigation is required to assess and analyze the variation in the bioavailability of flavonoids due to interactions with the intestinal barrier. This review will emphasize on the bioavailability and the pharmacological applications of flavonoids, key factors affecting their bioavailability, and strategies for enhancing bioavailability, which may lead to deeper understanding of the extent of flavonoids as a treatment and/or prevention for different diseases in clinics.
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http://dx.doi.org/10.1080/10408398.2021.1898333DOI Listing
April 2021

A strategy to differentiate dopamine and levodopa based on their cyclization reaction regulated by pH.

Anal Chim Acta 2021 May 12;1157:338379. Epub 2021 Mar 12.

Department of Chemistry, College of Sciences, Northeastern University, Shenyang, 110819, China. Electronic address:

Levodopa is often used to treat Parkinson's disease. It coexists with dopamine in human fluids and is electrochemically oxidized at the same potential as dopamine. Differentiating levodopa from dopamine is difficult via electrochemical techniques. Taking advantage of the differences in the rate constants of levodopa and dopamine for the intramolecular cyclization reaction, we observed that the cyclization reaction of dopamine-quinone was completely suppressed under pH 4.8, while that of levodopa-quinone occurred. The product of cyclization caused a new cathodic peak at negative potential. Its peak current was dependent on the concentration of levodopa but not that of dopamine. As a result, we developed a method of detecting levodopa in the presence of dopamine with a bare glassy carbon electrode.
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http://dx.doi.org/10.1016/j.aca.2021.338379DOI Listing
May 2021

Tumor suppressor role of hsa_circ_0035445 in gastric cancer.

J Clin Lab Anal 2021 Jun 8;35(6):e23727. Epub 2021 Apr 8.

The Affiliated People's Hospital, Ningbo University, Ningbo, China.

Circular RNAs (circRNAs) are closely related to the occurrence and development of cancers. However, the roles of circRNAs in gastric cancer are largely unknown. Total 104 pairs of gastric cancer tissues and non-cancer tissues, fasting plasma of 42 healthy people and 42 gastric cancer patients' one day before operation and 10 days after operation were collected. Quantitative reverse transcription-polymerase chain reaction was used to detect the expression level of hsa_circ_0035445. The receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) were used to analyze its diagnostic value. Small interfering RNA and overexpression vector were used to downregulate and upregulate the expression of hsa_circ_0035445, respectively. Cell Counting Kit-8 and colony formation assays were used to detect the proliferation ability. Trans-well assay and scratch assay were used to detect the migration ability. Finally, flow cytometry was used to detect the changes of cell cycle distribution and apoptosis. Hsa_circ_0035445 was lowly expressed in gastric cancer tissues, plasma of gastric cancer patients, and gastric cancer cells. The expression level of hsa_circ_0035445 in gastric cancer tissues was relationship with tumor size and distant metastasis. The AUC of hsa_circ_0035445 in tissues and plasma was 0.68 and 0.86, respectively. Upregulation of hsa_circ_0035445 suppressed the proliferation and migration, promoted apoptosis, and blocked cells at G0/G1 phase. Downregulation of hsa_circ_0035445 promoted the proliferation and migration, suppressed apoptosis, and blocked cells at S phase. In conclusion, hsa_circ_0035445 may become a new target for the treatment of gastric cancer.
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http://dx.doi.org/10.1002/jcla.23727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183929PMC
June 2021

Integrative Analysis of the Expression of SIGLEC Family Members in Lung Adenocarcinoma via Data Mining.

Front Oncol 2021 16;11:608113. Epub 2021 Mar 16.

Public Experimental Technology Center, The School of Basic Medical Science, Southwest Medical University, Luzhou, China.

Sialic acid-binding immunoglobulin-type lectin (SIGLEC) family members are involved in regulating immune-cell activation, proliferation, and apoptosis, and they play an important role in tumor development. However, their expression and correlation with immune molecules in lung adenocarcinoma (LUAD) remain unclear. We utilized Gene Expression Profiling Interactive Analysis, Kaplan-Meier analysis, the limma package in R/Bioconductor, the University of California Santa Cruz Cancer Genome Browser, cBioPortal, STRING, Cytoscape, DAVID, and the Tumor Immune Estimation Resource for gene and protein profiling and analyses. The results showed that SIGLEC10 and SIGLEC15 levels were upregulated in LUAD, whereas SIGLEC1, CD22 (SIGLEC2), CD33, myelin-associated glycoprotein (SIGLEC4), SIGLEC5, SIGLEC6, SIGLEC7, SIGLEC8, SIGLEC11, and SIGLEC14 levels were significantly downregulated, with their low expression associated with poor overall survival. Moreover, we observed high SIGLEC-mutation rates (22%) in LUAD patients, with SIGLEC functions determined as primarily involved in regulating the immune response, signal transduction, inflammatory response, and cell adhesion. Furthermore, we found that SIGLEC expression was significantly correlated with immune-cell infiltration, especially macrophages, neutrophils, and dendritic cells, and highly associated with immune molecules such as CD80, CD86, CD28, B-cell-activating factor, programmed cell death 1 ligand 2, and colony stimulating factor 1 receptor. These results provide insight into the potential molecular mechanism associated with SIGLEC-related development of LUAD, as well as clues for screening biomarkers and therapeutic targets.
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http://dx.doi.org/10.3389/fonc.2021.608113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008066PMC
March 2021

Clinical Application of Serum Inflammatory Factors Combined with Dynamic Detection in the Diagnosis and Treatment of Neonatal Sepsis.

Iran J Public Health 2021 Feb;50(2):325-332

Outpatient Department, Weifang People's Hospital, Weifang 261041, China.

Background: To investigate the clinical application value of the combination of the inflammatory factors and dynamic detection in the diagnosis and treatment of neonatal sepsis by detecting serum inflammatory factor C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) levels before and after treatment of neonatal infection.

Methods: A total of 138 neonates with different degrees of infection were randomly enrolled, including 88 cases in the sepsis group and 50 cases in the virus infection group. Another 50 non-infected newborns in the same period were enrolled as the normal control group. Venous blood of all subjects for CRP, PCT, IL-6 detection, and send bacterial blood culture for sepsis and virus infection groups were collected at the same time. In the recovery period, venous blood of children in sepsis group was collected again to review CRP, PCT, IL-6, and differences in each test index of each group were compared.

Results: The serum CRP, PCT, IL-6 levels in the sepsis group were significantly higher than those in the virus infection group (all <0.05); serum CRP, PCT, IL-6 levels in the sepsis group were significantly lower than before treatment ( <0.05); the sensitivity and accuracy of the combined detection of indicators for the diagnosis of neonatal sepsis were significantly improved.

Conclusion: The inflammatory factors CRP, PCT, and IL-6 are closely related to the occurrence and development of neonatal sepsis. Combined detection can effectively improve the diagnostic accordance rate, which is beneficial to the early diagnosis and early clinical intervention of neonatal sepsis.
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http://dx.doi.org/10.18502/ijph.v50i2.5347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956080PMC
February 2021

BMP5 silencing inhibits chondrocyte senescence and apoptosis as well as osteoarthritis progression in mice.

Aging (Albany NY) 2021 03 19;13(7):9646-9664. Epub 2021 Mar 19.

Department of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.

In this study, we using the destabilization of the medial meniscus (DMM) mouse model to investigate the role of bone morphogenetic protein 5 (BMP5) in osteoarthritis (OA) progression mediated via chondrocyte senescence and apoptosis. BMP5 expression was significantly higher in knee articular cartilage tissues of OA patients and DMM model mice than the corresponding controls. The Osteoarthritis Research Society International scores based on histological staining of knee articular cartilage sections were lower in DMM mice where BMP5 was knocked down in chondrocytes than the corresponding controls 4 weeks after DMM surgery. DMM mice with BMP5-deficient chondrocytes showed reduced levels of matrix-degrading enzymes such as MMP13 and ADAMTS5 as well as reduced cartilage destruction. BMP5 knockdown also decreased chondrocyte apoptosis and senescence by suppressing the activation of p38 and ERK MAP kinases. These findings demonstrate that BMP5 silencing inhibits chondrocyte senescence and apoptosis as well as OA progression by downregulating activity in the p38/ERK signaling pathway.
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http://dx.doi.org/10.18632/aging.202708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064147PMC
March 2021

Pilot study on long-term simulation of PCB-153 human body burden in the Tibetan Plateau.

Chemosphere 2021 Aug 6;276:130184. Epub 2021 Mar 6.

State Key Laboratory of Environmental Geochemistry, Institute of Geochemistry, Chinese Academy of Sciences, Guiyang, 550081, China. Electronic address:

The historical body burden of 2,2',4,4',5,5'-Hexachlorobiphenyl (PCB-153) in the Tibet Autonomous Region (TAR) population was simulated on the basis of localized exposure factors and dietary data, which present a preliminary attempt to quantify the influence of high lipid dietary patterns, grain transported from inland China, and atmospheric transport on human exposure to polychlorinated biphenyls (PCBs). Herdsman with large animal-based food consumption exhibited the highest body burden that was comparable with that in inland China. The body burden of other residents was within the range of low-to-moderate level. High-lipid diet of urban residents caused their body burden being 1.5--2.5 times higher than that of rural residents. The consumption of grain transported from higher polluted areas can also result in 50%-115% increase in the body burden of Tibetan rural residents compared with when local produced grain is consumed, suggesting that the influence of grain logistic can be as important as dietary patterns. The exposure risk for rural residents associated with grain logistic should not be ignored even if they consumed less high-lipid food. By splitting the inventory, over 80% of the PCB-153 pollution in the TAR was identified to be induced by atmospheric transport from foreign countries. However, the grain logistic contributed approximately half of the overall human body burden of Tibetan residents recently if assuming that the grain shortage was supplied by adjacent Sichuan Province. The combined influence of high-lipid diet, atmospheric transport and food logistic highlights the difficulties of risk control in remote regions that accumulate POPs, such as TAR.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130184DOI Listing
August 2021

Study on preparation, stability, thermal conductivity, and viscosity of silver nanoparticles-decorated three-dimensional graphene-like porous carbon hybrid nanofluids.

Nanotechnology 2021 Mar 10. Epub 2021 Mar 10.

School of Material and Energy, Guangdong University of Technology, Guangzhou, Guangdong, CHINA.

In the present study, a novel silver nanoparticles-decorated three-dimensional graphene-like porous carbon (Ag/3D GPC) nanocomposite has been synthesized via the method of carbonization and reduction of silver ions at the same time. This Ag/3D GPC nanocomposite possess an interconnected network of well crystalized and submicron-sized macropores with thin graphene walls of several nanometers, where silver nanoparticles distributing uniformly. The water based and ethylene glycol based Ag/3D GPC hybrid nanofluids have been prepared without any surfactant. The hybrid nanofluids with low concentration (<0.8 wt%) can be steadily dispersed for more than six months. The thermal conductivity enhancement for the nanofluids with 0.1 wt% can reach 10.3% and 8.8% at 25℃ compared with pure water and ethylene glycol, respectively. The viscosity of nanofluids is investigated, the temperature dependence of the dynamic viscosity obeys an Arrhenius-like behavior. The prepared Ag/3D GPC hybrid nanofluids with good stability and thermal conductivity are promisingly considered to be used in heat transfer field.
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http://dx.doi.org/10.1088/1361-6528/abed77DOI Listing
March 2021

GSK3 inhibitor ameliorates steatosis through the modulation of mitochondrial dysfunction in hepatocytes of obese patients.

iScience 2021 Mar 6;24(3):102149. Epub 2021 Feb 6.

Department of Cell Biology, School of Basic Medical Science, Capital Medical University, Beijing, 100069, China.

Obesity is an important risk factor and a potential treatment target for hepatic steatosis. The maladaptation of hepatic mitochondrial flexibility plays a key role in the hepatic steatosis. Herein, we found that hepatocyte-like cells derived from human adipose stem cell of obese patients exhibited the characteristics of hepatic steatosis and accompanied with lower expression of the subunits of mitochondrial complex I and lower oxidative phosphorylation levels. The GSK3 inhibitor CHIR-99021 promoted the expression of NDUFB8, NDUFB9, the subunits of mitochondrial complex I, the basal oxygen consumption rate, and the fatty acid oxidation of the hepatocytes of obese patients by upregulating the expression of the transcription factor PGC-1α, TFAM, and NRF1 involved in mitochondrial biogenesis. Moreover, CHIR-99021 decreased the lipid droplets size and the triglyceride levels in hepatocytes of obese patients. The results demonstrate that GSK3 inhibition ameliorates hepatic steatosis by elevating the mitochondrial function in hepatocytes of obese patients.
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http://dx.doi.org/10.1016/j.isci.2021.102149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900441PMC
March 2021

LXRα/β Antagonism Protects against Lipid Accumulation in the Liver but Increases Plasma Cholesterol in .

Chem Res Toxicol 2021 Mar 1;34(3):833-838. Epub 2021 Mar 1.

School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Nonalcoholic fatty liver disease (NAFLD) is characterized by lipid accumulation in the liver and associates with obesity, hyperlipidemia, and insulin resistance. NAFLD could lead to nonalcoholic steatohepatitis (NASH), hepatic fibrosis, cirrhosis, and even cancers. The development of therapy for NAFLD has been proven difficult. Emerging evidence suggests that liver X receptor (LXR) antagonist is a potential treatment for fatty liver disease. However, concerns about the cholesterol-increasing effects make it questionable for the development of LXR antagonists. Here, the overweight monkeys were fed with LXRβ-selective antagonist sophoricoside or LXRα/β dual-antagonist morin for 3 months. The morphology of punctured liver tissues was examined by H&E staining. The liver, heart, and kidney damage indices were analyzed using plasma. The blood index was assayed using complete blood samples. We show that LXRβ-selective antagonist sophoricoside and LXRα/β dual-antagonist morin alleviated lipid accumulation in the liver in overweight monkeys. The compounds resulted in higher plasma TC or LDL-c contents, increased white blood cell and lymphocyte count, and decreased neutrophile granulocyte count in the monkeys. The compounds did not alter plasma glucose, apolipoprotein A (ApoA), ApoB, ApoE, lipoprotein (a) (LPA), nonesterified fatty acid (NEFA), aspartate transaminases (AST), creatinine (CREA), urea nitrogen (UN), and creatine kinase (CK) levels. Our data suggest that LXRβ-selective and LXRα/β dual antagonism may lead to hypercholesterolemia in nonhuman primates, which calls into question the development of LXR antagonist as a therapy for NAFLD.
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http://dx.doi.org/10.1021/acs.chemrestox.0c00445DOI Listing
March 2021

Bornyl Diphosphate Synthase From and Its Application for (+)-Borneol Biosynthesis in Yeast.

Front Bioeng Biotechnol 2021 11;9:631863. Epub 2021 Feb 11.

State Key Laboratory Breeding Base of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.

(+)-Borneol is a desirable monoterpenoid with effective anti-inflammatory and analgesic effects that is known as soft gold. (+)-bornyl diphosphate synthase is the key enzyme in the (+)-borneol biosynthesis pathway. Despite several reported (+)-bornyl diphosphate synthase genes, relatively low (+)-borneol production hinders the attempts to synthesize it using microbial fermentation. Here, we identified the highly specific (+)-bornyl diphosphate synthase CbTPS1 from . An assay showed that (+)-borneol was the main product of CbTPS1 (88.70% of the total products), and the value was 5.11 ± 1.70 μM with a value of 0.01 s. Further, we reconstituted the (+)-borneol biosynthetic pathway in . After tailored truncation and adding Kozak sequences, the (+)-borneol yield was improved by 96.33-fold to 2.89 mg⋅L compared with the initial strain in shake flasks. This work is the first reported attempt to produce (+)-borneol by microbial fermentation. It lays a foundation for further pathway reconstruction and metabolic engineering production of this valuable natural monoterpenoid.
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http://dx.doi.org/10.3389/fbioe.2021.631863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905068PMC
February 2021

Evidence of Foodborne Transmission of the Coronavirus (COVID-19) through the Animal Products Food Supply Chain.

Environ Sci Technol 2021 03 16;55(5):2713-2716. Epub 2021 Feb 16.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

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http://dx.doi.org/10.1021/acs.est.0c06822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927281PMC
March 2021

Nursing resources and patient outcomes in intensive care units: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Feb;100(6):e24507

Department of Internal Medicine, North Hospital, Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Lanzhou city, Gansu province, China.

Background: As nursing resources is directly related to patient outcomes in the intensive care unit setting, identifying factors related to nursing resources at various levels could contribute to improving those outcomes. This study aims to determine the association of nursing resources with outcomes of intensive care unit patients.

Method: This study adheres to the Preferred Reporting Items for Systematic Reviews and Meta-analysis for Protocols. Chinese electronic Database (Chinese Biomedical Literature Database, Wanfang, and China National Knowledge Infrastructure) and international electronic databases (PubMed, Embase, Cochrane Library, and Web of Science) will be searched for all relevant published articles, with no restrictions on the year of publication or language. Study selection, data collection and assessment of study bias will be conducted independently by a pair of independent reviewers. The Newcastle-Ottawa Scale tool will be used for the risk of bias assessment. The Grading of Recommendations Assessment Development and Evaluation system will be used to assess the quality of evidence. The statistical analysis of this meta-analysis will be calculated by Review manager version 5.3.

Results: The results of this study will be published in a peer-reviewed journal.

Conclusion: The findings of this systematic review will provide a high-quality synthesis of latest evidence and provide a basis for assessing the association of nursing resources on patients' outcomes in intensive care units.

Trial Registration Number: 10.17605/OSF.IO/9FNEX.
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http://dx.doi.org/10.1097/MD.0000000000024507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886425PMC
February 2021

Kinetics-Driven Drug Design Strategy for Next-Generation Acetylcholinesterase Inhibitors to Clinical Candidate.

J Med Chem 2021 02 11;64(4):1844-1855. Epub 2021 Feb 11.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, People's Republic of China.

The acetylcholinesterase (AChE) inhibitors remain key therapeutic drugs for the treatment of Alzheimer's disease (AD). However, the low-safety window limits their maximum therapeutic benefits. Here, a novel kinetics-driven drug design strategy was employed to discover new-generation AChE inhibitors that possess a longer drug-target residence time and exhibit a larger safety window. After detailed investigations, compound was identified as a highly potent, highly selective, orally bioavailable, and brain preferentially distributed AChE inhibitor. Moreover, it significantly ameliorated cognitive impairments in different mouse models with a lower effective dose than donepezil. The X-ray structure of the cocrystal complex provided a precise binding mode between and AChE. Besides, the data from the phase I trials demonstrated that had good safety, tolerance, and pharmacokinetic profiles at all preset doses in healthy volunteers, providing a solid basis for its further investigation in phase II trials for the treatment of AD.
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http://dx.doi.org/10.1021/acs.jmedchem.0c01863DOI Listing
February 2021