Publications by authors named "Jianping Zhou"

372 Publications

Experimental Diagnosis on Combustion Characteristic of Shock Wave Focusing Initiation Engine.

Entropy (Basel) 2022 Jul 21;24(7). Epub 2022 Jul 21.

Science and Technology on Plasma Dynamics Laboratory, Air Force Engineering University, Xi'an 710038, China.

A shock wave focusing initiation engine was assembled and tested in an experimental program. The effective pyrolysis rate of the pre-combustor was evaluated over a range of supplementary fuel ratio in this paper. Results highlight two operational modes of the resonant cavity: (1) pulsating combustion mode, (2) stable combustion mode. The appearance of the two combustion modes is jointly affected by the flow and the structural characteristic value of the combustion chamber. This paper uses images, time-frequency analysis, and nonlinear time series analysis methods to identify and distinguish these two combustion modes. It is believed that the interaction between the combustion chamber and the supply plenum is the probable reason for different combustion modes. The experiment has found that structural parameters and import flow parameters have an impact on the initiation of the combustion chamber. Increasing the injection pressure can appropriately broaden the fuel-rich boundary of initiation. Low equivalence ratio and high injection pressure can also appropriately increase the combustion working frequency in a small range. From the perspective of pressure utilization, under the premise of ensuring successful initiation, injection pressure should not be too high.
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http://dx.doi.org/10.3390/e24071007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9321480PMC
July 2022

Charge reversal hairpin peptide modified synergy therapeutic nanoplatforms for tumor specific drug shuttling.

Biomater Sci 2022 Jul 21. Epub 2022 Jul 21.

State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.

Given the distinct pathological features of neoplasm tissues, multifunctional responsive nanocarriers have been recently considered as promising candidates to optimize the chemotherapy regime. As a result, we propose a graphene oxide-based pH-responsive drug delivery system covalent assembly of "hairpin-like" cell penetrating peptides with acid sensitive and charge reversal properties to realize superior tumor specificity and lower toxicity. Graphene oxide here can serve as high doxorubicin-loading nanosheets and facilitate swift drug release in response to laser irradiation, which provides an efficient platform for the synergy of photo-chemotherapy. Structurally, polyglycol conjugation on the graphene oxide surface fulfils the function of nanocomposite stabilization. After administration, the elaborately acid sensitive cell penetrating peptides maintain the hairpin structure under physiological conditions, while after entering the tumor acidic microenvironment, they undergo charge reversal and structural conversion to promote the cellular uptake of nanoparticles. The evaluation of nanocomposites revealed their negligible systematic toxicity and remarkable antitumor effects. experiments also confirmed the impressive stability and tumor-specific targeting for alleviating breast cancer. In conclusion, hairpin peptide modified graphene oxide nanoparticles show multiple merits including high drug carrying capacity, selective tumor penetration, responsive drug release and effective combination oncotherapy.
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http://dx.doi.org/10.1039/d2bm00817cDOI Listing
July 2022

Preliminary Study of an Adjustable, Wearable, Noninvasive Vest Providing Chest Compression to Assist with Breathing.

J Biomed Nanotechnol 2022 Apr;18(4):1172-1179

Department of Spine Surgery, Thoracic and Cardiovascular Surgery and Anesthesiology, Dongguan People's Hospital/Affiliated Dongguan Hospital, Southern Medical University, Dongguan, Guangdong, 523069, China.

Respiratory muscle paralysis caused by acute cervical spinal cord injury usually leads to pulmonary ventilation dysfunction and even death from respiratory failure. In addition to invasive treatments such as mechanical ventilation, the utilization of noninvasive respiratory support equipment plays an important role in long-term assisted breathing. In this study, we describes a wearable, noninvasive vest with adjustable pressure that enables assisted breathing and with an automatic alarm, and we aims to explore its safety and effectiveness on healthy adult participants. The vest monitors the human heart rate and the blood oxygen index data in real time, the alarm is automatically activated when the data is abnormal. Eight healthy participants had no obvious discomfort during the test while wearing the vest. Lung volumes, antero-posterior diameters, and left-right diameters at the second, fourth, and sixth ribs levels were acquired before and after inflation of the vest airbag, the data acquired by the imaging analysis using chest computed tomography showed significant differences before and after the inflation ( < 0.05). Thus, The vest designed for this study can achieve uniform and effective compression of the thorax, significantly changed the size of the thorax and lungs. It is expected to be applied as noninvasive support for patients with respiratory dysfunction.
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http://dx.doi.org/10.1166/jbn.2022.3323DOI Listing
April 2022

The Characterization of Microbiome and Interactions on Weathered Rocks in a Subsurface Karst Cave, Central China.

Front Microbiol 2022 29;13:909494. Epub 2022 Jun 29.

Department of Microbiology, The Ohio State University, Columbus, OH, United States.

Karst caves are a natural oligotrophic subsurface biosphere widely distributed in southern China. Despite the progress in bacterial and fungal diversity, the knowledge about interactions between bacteria, fungi, and minerals is still limited in caves. Hence, for the first time, we investigated the interaction between bacteria and fungi living on weathered rocks in the Heshang Cave high-throughput sequencing of 16S rRNA and ITS1 genes, and co-occurrence analysis. The mineral compositions of weathered rocks were analyzed by X-ray diffraction. Bacterial communities were dominated by (33.68%), followed by (8.78%), and (8.73%). In contrast, fungal communities were dominated by (21.08%) and (14.06%). Mineral substrata, particularly phosphorus-bearing minerals, significantly impacted bacterial (hydroxyapatite) and fungal (fluorapatite) communities as indicated by the redundancy analysis. In comparison with fungi, the development of bacterial communities was more controlled by the environmental selection indicated by the overwhelming contribution of deterministic processes. Co-occurrence network analysis showed that all nodes were positively linked, indicating ubiquitous cooperation within bacterial groups and fungal groups, as well as between bacteria and fungi under oligotrophic conditions in the subsurface biosphere. In total, 19 bacterial ASVs and 34 fungal OTUs were identified as keystone taxa, suggesting the fundamental role of fungi in maintaining the microbial ecosystem on weathered rocks. was most dominant in keystone taxa, accounting for 26.42%, followed by in bacteria (24.53%). Collectively, our results confirmed the highly diverse bacterial and fungal communities on weathered rocks, and their close cooperation to sustain the subsurface ecosystem. Phosphorus-bearing minerals were of significance in shaping epipetreous bacterial and fungal communities. These observations provide new knowledge about microbial interactions between bacteria, fungi, and minerals in the subterranean biosphere.
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http://dx.doi.org/10.3389/fmicb.2022.909494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277220PMC
June 2022

Efficacy, prognosis and safety analysis of anti-PD-1/PD-L1 inhibitor rechallenge in advanced lung cancer patients: a cohort study.

Transl Lung Cancer Res 2022 Jun;11(6):1038-1050

Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: The rechallenge of immune checkpoint inhibitors (ICI) is now an optional strategy for patients who discontinued ICI due to immune-related adverse events (irAEs) or disease progression. However, little data is available for the prognosis and prognostic factors of patients receiving ICI rechallenge treatment in advanced lung cancer patients. Our study aimed to explore the efficacy, prognosis and safety of patients who received anti-programmed cell death-1/programmed cell death ligand 1 (anti-PD-1/PD-L1) inhibitor rechallenge.

Methods: In our retrospective cohort study, data of advanced lung cancer patients who received anti-PD-1/PD-L1 inhibitor and discontinued due to irAEs or disease progression were collected from December 2016 to August 2021. Enrolled patients were categorized into two groups: rechallenge group (R group) and non-rechallenge group (NR group). Progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety data were analyzed. Cox model and subgroup analysis were analyzed according to baseline characteristics, ICI type, the reason for discontinuing ICI, etc. According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), evaluation was performed routinely every 6-8 weeks after initiating treatment with the PD-1/PD-L1 inhibitor. The last follow-up in the study was on September 20, 2021.

Results: Eighty-one patients who met our inclusion criteria were enrolled. In the whole cohort, the R group achieved better OS than the NR group [hazard ratio (HR) =0.176; 95% confidence interval (CI): 0.065-0.477; P=0.001). In the irAEs group, the survival analyses showed a trend toward improved OS in the rechallenge subgroup (HR =0.287; 95% CI: 0.081-1.025; P=0.055), and a promising DCR of 75% after an ICI rechallenge. Additionally, the exploration of safety outcomes indicated an acceptable recurrence rate (22.5%) of irAEs and an early onset of irAEs after an ICI rechallenge. In the disease progression group, the rechallenge subgroup did not improve OS (HR =0.214; 95% CI: 0.027-1.695; P=0.144), and the DCR of the rechallenge subgroup was 40% after ICI rechallenge.

Conclusions: ICI rechallenge might be an attractive option for patients who discontinue treatment due to irAEs. For patients with disease progression, further research should be conducted. The recurrence of irAEs and their early onset during the second round of ICI should be considered.
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http://dx.doi.org/10.21037/tlcr-22-360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271445PMC
June 2022

Multi-leader-follower group consensus of stochastic time-delay multi-agent systems subject to Markov switching topology.

Math Biosci Eng 2022 May;19(8):7504-7520

School of Computer Science & Technology, Anhui University of Technology, Ma'anshan 243032, China.

The multi-leader-follower group consensus issue of a class of stochastic time-delay multi-agent systems subject to Markov switching topology is investigated. The purpose is to determine a distributed control protocol to make sure that the followers' states converge in mean square to a convex hull generated by the leaders' states. Through a model transformation, the problem is transformed into a mean-square stability issue of a new system. Then, an easy-to-check sufficient condition for the solvability of the multi-leader-follower group consensus issue is proposed by utilizing the Lyapunov stability theory, graph theory, as well as several inequality techniques. It is shown that the required feedback gain can be acquired once the condition is satisfied. Finally, an example is used to illustrate the effectiveness of the control protocol.
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http://dx.doi.org/10.3934/mbe.2022353DOI Listing
May 2022

Subxiphoid and subcostal arch versus unilateral video-assisted thoracic surgery approaches to thymectomy for myasthenia gravis.

Surg Today 2022 Jul 1. Epub 2022 Jul 1.

Department of Thoracic and Cardiovascular Surgery, Affiliated Dongguan People's Hospital, Southern Medical University (Dongguan People's Hospital), No. 3, South of Wandao Road, Wanjiang District, Dongguan, 523000, China.

Purpose: Thymectomy is an important treatment for myasthenia gravis (MG). We conducted this study to compare the clinical outcomes of the recently introduced subxiphoid and subcostal arch thymectomy (SASAT) approach with those of the standard unilateral video-assisted thoracoscopic surgery (VATS).

Methods: We analyzed, retrospectively, the perioperative, and long-term outcomes of 179 consecutive MG patients (age 18-65 years), who underwent SASAT or unilateral VATS-extended thymectomy between July, 2012 and May, 2019.

Results: All demographic and clinical characteristics were comparable in the two groups. The median surgical time, estimated blood loss, thoracotomy conversion rate, total and chest drainage, and complications did not differ significantly between the groups. The visual analog scale (VAS) score was significantly lower in the SASAT group. Complete stable remission (CSR) was achieved in a significantly larger proportion of the SASAT group patients and was significantly higher in women than in men. The Quantitative MG score was significantly lower in the SASAT group. Patients in the MG Foundation of America Clinical Classification groups I and II achieved better remission rates than those in groups III-V.

Conclusions: SASAT is a safe and feasible MG treatment, which may yield better outcomes than unilateral VATS and improve the quality of treatment.
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http://dx.doi.org/10.1007/s00595-022-02533-4DOI Listing
July 2022

Amine-Directed Formation of B-N Bonds for BN-Fused Polycyclic Aromatic Multiple Resonance Emitters with Narrowband Emission.

Angew Chem Int Ed Engl 2022 Jun 24:e202207293. Epub 2022 Jun 24.

Key Lab of Organic Optoelectronics and Molecular Engineering of Ministry of Education, Department of Chemistry, Tsinghua University, Beijing, 100084, P. R. China.

Despite the remarkable multiple resonance (MR) optoelectronic properties of organic nanographenes with boron and nitrogen atoms disposed para to each other, the synthetic procedures are sophisticated with low yields and the molecular skeletons are limited. Here, a new paradigm of easy-to-access MR emitter is constructed by simplifying the multiborylation through amine-directed formation of B-N bonds while introducing an additional para-positioned nitrogen atom to trigger the MR effect. The proof-of-concept molecules exhibit narrowband emissions at 480 and 490 nm, with full width at half maxima (FWHMs) of only 29 and 34 nm. The devices based on them showed external quantum efficiencies (EQE) of >33.0 %, which remained above 24.0 % even at a high brightness of 5000 cd m . This is the first example of MR emitters with a B-N covalent bond, not only decreasing the synthesis difficulty but also increasing the diversity of MR skeletons for emerging new optoelectronic properties.
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http://dx.doi.org/10.1002/anie.202207293DOI Listing
June 2022

Biofunctionalized graphene oxide nanosheet for amplifying antitumor therapy: Multimodal high drug encapsulation, prolonged hyperthermal window, and deep-site burst drug release.

Biomaterials 2022 Jun 9;287:121629. Epub 2022 Jun 9.

Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education), State Key Laboratory of Natural Medicines, NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China. Electronic address:

Biofunctional surface-modification surpassed critical limitation of graphene oxide (GO) in biocompatibility and drug delivery efficiency, contributing to versatile biomedical applications. Here, a protein corona-bridged GO nanoplatform with high drug loading, longstanding hyperthermia, and controllable drug release, was engineered for amplified tumor therapeutic benefits. Structurally, GO surface was installed with phenylboronic acid (PBA) layer, on which iRGD conjugated apolipoprotein A-I (iRGD-apoA-I) was coordinated via boron electron-deficiency, to form the sandwich-like GO nanosheet (iAPG). The GO camouflaging by iRGD-apoA-I corona provided multimodal high doxorubicin (DOX) loading by π-π stacking and coordination, and generated a higher photothermal transformation efficiency simultaneously. In vitro studies demonstrated that iAPG significantly improved drug penetration and internalization, then achieved tumor-targeted DOX release through near-infrared (NIR) controlled endo/lysosome disruption. Moreover, iAPG mediated site-specific drug shuttling to produce a 3.53-fold enhancement of tumor drug-accumulation compared to the free DOX in vivo, and induced deep tumor penetration dramatically. Primary tumor ablation and spontaneous metastasis inhibition were further demonstrated with negligible side effects under optimal NIR. Taken together, our work provided multifunctional protein corona strategy to inorganic nanomaterials toward advantageous biomedical applications.
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http://dx.doi.org/10.1016/j.biomaterials.2022.121629DOI Listing
June 2022

Age-related variations in position and morphology of the temporomandibular joint in individuals with anterior openbite and crossbite: a multi-cross-sectional comparative study.

BMC Oral Health 2022 05 23;22(1):200. Epub 2022 May 23.

Stomatological Hospital of Chongqing Medical University, 426 Songshi North Road, Chongqing, China.

Background: This study aimed to compare the age-related positional and morphological characteristics of the temporomandibular joint (TMJ) between individuals with anterior openbite or crossbite and controls.

Methods: This multi-cross-sectional comparative study analysed cone-beam computed tomography images of 750 participants, equally divided into the openbite, crossbite, and control groups (OBG, CBG, and CG, respectively). Each group was further divided into five subgroups (8-11 years, 12-15 years, 16-19 years, 20-24 years, and 25-30 years). Measurements of the TMJ included the position of the condyles in their respective fossae and morphology of the condyles and fossae. Data were submitted to statistical analysis. The study adhered to the STROBE Statement checklist for reporting of cross-sectional studies.

Results: Condyles were positioned more posteriorly with increasing age in all groups, and the condylar position was more posterior in the OBG than in the CBG. The articular eminence inclination increased with age in all the groups. There were significant differences in the articular eminence inclination among the three major groups at the age of > 15 years, and the condylar path was flatter in the CBG than in the OBG.

Conclusions: Age-related morphological and positional characteristics of the TMJ differed considerably among OBG, CBG and CG. Contrary to CBG, OBG was found to have relatively posterior condylar position and steeper condylar path.
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http://dx.doi.org/10.1186/s12903-022-02236-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9125888PMC
May 2022

Genome-wide analyses of PAM-relaxed Cas9 genome editors reveal substantial off-target effects by ABE8e in rice.

Plant Biotechnol J 2022 May 6. Epub 2022 May 6.

Jiangsu Key Laboratory of Crop Genomics and Molecular Breeding/Jiangsu Key Laboratory of Crop Genetics and Physiology, Agricultural College of Yangzhou University, Yangzhou, China.

PAM-relaxed Cas9 nucleases, cytosine base editors and adenine base editors are promising tools for precise genome editing in plants. However, their genome-wide off-target effects are largely unexplored. Here, we conduct whole-genome sequencing (WGS) analyses of transgenic plants edited by xCas9, Cas9-NGv1, Cas9-NG, SpRY, nCas9-NG-PmCDA1, nSpRY-PmCDA1 and nSpRY-ABE8e in rice. Our results reveal that Cas9 nuclease and base editors, when coupled with the same guide RNA (gRNA), prefer distinct gRNA-dependent off-target sites. De novo generated gRNAs by SpRY editors lead to additional, but insubstantial, off-target mutations. Strikingly, ABE8e results in ~500 genome-wide A-to-G off-target mutations at TA motif sites per transgenic plant. ABE8e's preference for the TA motif is also observed at the target sites. Finally, we investigate the timeline and mechanism of somaclonal variation due to tissue culture, which chiefly contributes to the background mutations. This study provides a comprehensive understanding on the scale and mechanisms of off-target and background mutations occurring during PAM-relaxed genome editing in plants.
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http://dx.doi.org/10.1111/pbi.13838DOI Listing
May 2022

MicroRNA-384-5p protects against cardiac hypertrophy via the ALPK3 signaling pathway.

J Biochem Mol Toxicol 2022 May 5:e23093. Epub 2022 May 5.

The Department of Thoracic, Dongguan People's Hospital, Dongguan, Guangdong, China.

Heart failure is a condition caused by a variety of pathophysiological factors. One important pathological change of chronic heart failure is myocardial hypertrophy. In recent years, several studies have found that dysregulated microRNAs are involved in regulating the pathological process of heart failure. In this study, cardiac hypertrophy models were constructed using isoproterenol (ISO)-/angiotensin-II (Ang-II) to explore the role of miR-384-5p in cardiac hypertrophy and its molecular mechanism in vivo and in vitro. Echocardiography, invasive pressure-volume analysis and hematoxylin-eosin staining were used to explore cardiac structure and function. ALPK3 mRNA and protein expression were detected using quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blot analysis and miR-384-5p expression were assessed via RT-qPCR. Our findings determined that miR-384-5p was notably decreased in cardiac hypertrophic tissues and cells, and overexpression of miR-384-5p could ameliorate pressure overload. Furthermore, ALPK3 was determined to downregulate the ALPK3 expression to aggravate cardiomyocyte hypertrophy. Our findings provided a potential therapeutic target for the treatment of cardiac hypertrophy.
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http://dx.doi.org/10.1002/jbt.23093DOI Listing
May 2022

New insights into the diagnostic characteristics and clinical application of serum biomarkers for lung cancer, and human epididymis protein 4 as a new biomarker?

Neoplasma 2022 May 26;69(3):729-740. Epub 2022 Apr 26.

Division of In Vitro Diagnostics, Shenzhen Mindray Bio-Medical Electronics Corporation, Shenzhen, Guangdong, China.

The value of serum tumor biomarkers used for lung cancer diagnosis is still controversial in clinical practice. This study aimed to further dissect and evaluate the clinical value of serum progastrin-releasing peptide (ProGRP), neuron-specific enolase (NSE), squamous cell carcinoma antigen (SCC-Ag), carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA21-1) together with a potential new biomarker, the human epididymis protein 4 (HE4) for lung cancer diagnosis, in a large cohort of a Chinese population. Ostensibly healthy individuals, as well as those with benign non-cancerous diseases, benign tumors, lung cancers, and other types of malignancies, were enrolled in the study. Serum ProGRP, NSE, SCC-Ag, CEA, CYFRA21-1, and HE4 were analyzed using the chemiluminescence immunoassay. Data were analyzed utilizing the SPSS and GraphPad Prism software. Detailed dissection of the diagnostic characteristics of serum 6 biomarkers on lung cancer was performed. All 6 biomarkers showed capabilities in characterizing lung cancer from other diseases. ProGRP and NSE were highly specific to small cell lung cancer (SCLC); SCC-Ag was a fair biomarker for NSCLC, specifically SCC histotype; CEA showed specificity to SCLC, followed by NSCLC; CYFRA21-1 was a good biomarker for both SCLC and NSCLC; HE4 showed high specificity to SCLC. For NSCLC characterization, CYFRA21-1+HE4+CEA was the best combinatory pattern in the terms of diagnostic performance (AUC=0.8110). The best combinatory analysis for SCLC was ProGRP+NSE+HE4 (AUC=0.9282). Patients with advanced stage, larger tumor, males, and age 50 or older had higher serum biomarkers levels than those with early stage, smaller tumor, females, and age under 50. Six biomarkers had capabilities in characterizing lung cancer with high or fair diagnostic performance. HE4 is a potential biomarker for both SCLC and NSCLC diagnosis, which merits further investigation.
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http://dx.doi.org/10.4149/neo_2022_220207N144DOI Listing
May 2022

The programmed site-specific delivery of LY3200882 and PD-L1 siRNA boosts immunotherapy for triple-negative breast cancer by remodeling tumor microenvironment.

Biomaterials 2022 05 12;284:121518. Epub 2022 Apr 12.

State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, NO.639 Longmian Avenue, Nanjing, 211198, China. Electronic address:

Despite the remarkable success of immunotherapies over the past decade, their effectiveness against triple-negative breast cancer (TNBC) is limited to a small subset of patients, mainly due to the low immunogenicity and unfavorable tumor microenvironment. In this study, we successfully constructed a programmed site-specific delivery nanosystem for the combined delivery of transforming growth factor beta (TGF-β) receptor inhibitor LY3200882 (LY) and PD-L1 siRNA (siPD-L1) to boost anti-tumor immunotherapy. As expected, LY in the outer layer of the nanosystem was released by stimulation of MMP2, and dramatically down-regulated the expression of extracellular matrix (ECM) in the tumor-associated fibroblasts (TAFs), and thus promoted the infiltration of effector T cells and penetration of nanomedicines. Simultaneously, the blockade of TGF-β by LY also triggered immunogenic cell death (ICD) of tumor cells and induced the maturation of dendritic cells. Moreover, the programmed design provided the siPD-L1/protamine cationic inner core with easier access to tumor cells and TAFs after MMP2-stimulated breakup of the outer layer, down-regulating the expression of PD-L1 in both types of cells. Notably, the synergistic effect of LY and siPD-L1 remarkably enhanced the tumor antigen presentation and immunosuppressive microenvironment remodeling, thus efficiently inhibiting the TNBC growth, metastasis, and recurrence. Therefore, the programmed site-specific delivery nanosystem is a promising drug delivery platform for boosting anti-tumor immunotherapy efficacy for TNBC.
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http://dx.doi.org/10.1016/j.biomaterials.2022.121518DOI Listing
May 2022

Methylsulfonylmethane protects against lethal dose MRSA-induced sepsis through promoting M2 macrophage polarization.

Mol Immunol 2022 06 20;146:69-77. Epub 2022 Apr 20.

Department of Wound Infection and Drug, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing 400042, PR China. Electronic address:

Background: Multi-drug-resistant bacterial infections, which have become a global threat, lack effective treatments. The discoveries of non-antibiotics with different modes of antibacterial action, such as methylsulfonylmethane (MSM), are a promising new treatment for multi-drug-resistant pathogens.

Methods: We constructed a mouse peritonitis infection model to evaluate the effects of MSM against methicillin-resistant Staphylococcus aureus (MRSA) infection. The time-kill kinetics of MSM against MRSA and the effect of MSM on the integrity of bacterial cell membrane were measured. Viability effects of MSM on THP1 cells were performed by CCK-8 cytotoxicity assay. Systematic inflammatory factor levels of mice were detected using ELISA. The immune response of peritoneal macrophages during MRSA-infection was evaluated using RNA sequencing. Gene Ontology function, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses, and correlation analyses were applied to analysis RNA sequencing data. RT-qPCR, western blotting and flow cytometry were performed to analysis the gene and protein expression levels of macrophages.

Results: In in vitro experiments, MSM did not show significant killing effects on the growth of MRSA directly and did not destroy bacterial membrane integrity. MSM also displayed no significant effects on the proliferative capacity of THP1 cells. However, MSM treatment protected mice against a lethal dose MRSA-infection and decreased systemic inflammation. MSM upregulated metabolic pathway in peritoneal macrophages, especial glycolysis, during MRSA infection. MSM increased the expression of M2 markers (such as Arg1), promoted phosphorylation of STAT3 (which regulates M2 polarization), and decreased the expression of M1 markers in peritoneal macrophages. Additionally, MSM treatment increased the expression of H3K18 lactylation specific target genes, including Arg1. GNE-140, the LDHA-specific inhibitor of glycolysis, blocked the MSM-induced Arg1 expression in this disease model.

Conclusions: MSM protects against MRSA infection through immunomodulation. MSM promotes the expression of Arg1 by lactate-H3K18la pathway to control macrophage to M2 polarization; it firstly provides therapeutic potential for drug-resistant infections and sepsis.
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http://dx.doi.org/10.1016/j.molimm.2022.04.001DOI Listing
June 2022

Correction to: Expression of osteoprotegerin and receptor activator of nuclear factor κB ligand in root resorption induced by heavy force in rats.

J Orofac Orthop 2022 Jul;83(4):285

Department of Orthodontics, The affiliated Hospital of Stomatology, Chongqing Medical University, Chongqing, China.

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http://dx.doi.org/10.1007/s00056-022-00396-5DOI Listing
July 2022

Correction to: Effect of EMD on the orthodontically induced root resorption repair process in rats.

J Orofac Orthop 2022 May;83(3):221

Department of Orthodontics, College of Stomatology, Chongqing Medical University, Chongqing, China.

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http://dx.doi.org/10.1007/s00056-022-00390-xDOI Listing
May 2022

Tumor-oriented mathematical models in hydrogel regulation for precise topical administration regimens.

J Control Release 2022 05 24;345:610-624. Epub 2022 Mar 24.

Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education), State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.. Electronic address:

Increasing knowledge of drug delivery properties, tumor profiles and their relationship promotes precise administration regimens, representing a promising pattern to personalized tumor treatment. Herein, we propose a regulatory hydrogel depot toward metastatic cancer by establishing mathematical models between tumor characteristics and administration regimens. Specifically, a thermo-sensitive PLGA-PEG-PLGA polymer is introduced as injectable hydrogel matrix, of which the administration volume and frequency are manipulated elaborately according to tumor size and gel-degradation kinetics. Structurally, doxorubicin (Dox) and arginine-terminated nanoparticles containing KIAA1199 specific shRNA (RPDNs) are incorporated into hydrogels, thereby formulating a topical and sustained drug depot to achieve synergy treatment. For dual-targeting therapy, Dox interdicts DNA replication/transcription, and shKIAA persistently silences KIAA1199 protein to modulate aggressive phenotypes. After individual peritumoral injection, Gel/RPDNs/Dox demonstrates desirable distribution patterns and gel degradation kinetics with enhanced tumor penetration. Moreover, a preferable inhibition of tumor proliferation and metastasis is confirmed after twice treatment in 12 days, indicating better therapeutic efficacy with less dosage and frequency. Consequently, the controllable administration regimen inspired mathematical models of thermosensitive hydrogel provides an intelligent platform for personalized treatment to metastatic cancer.
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http://dx.doi.org/10.1016/j.jconrel.2022.03.042DOI Listing
May 2022

Retraction: Multifunctional Polymeric Nanosystems for Dual-Targeted Combinatorial Chemo/Antiangiogenesis Therapy of Tumors.

Adv Healthc Mater 2022 Apr 25;11(8):e2200329. Epub 2022 Mar 25.

Adv. Healthcare Mater. 2016, 5, 1447-1461 DOI: 10.1002/adhm.201600169 The above article, published online on 29 April 2016 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal's Editor-in-Chief, Dr. Uta Goebel, and Wiley-VCH GmbH. Concerns about figures within this article were raised by a reader in 2021, which has led to two Corrections of this article published on 20 January 2021 and 21 October 2021, respectively. Subsequently, further concerns were raised about another figure within the article and an investigation of these new concerns indicated that there have been some modifications of the figures that cannot easily be explained. As a result, the journal is unable to determine whether the results and conclusions are valid and so have made the decision to retract the article. [1] F. Z. Dahmani, Y. Xiao, J. Zhang, Y. Yu, J. Zhou, J. Yao, Adv. Healthcare Mater. 2021, 10, 2002223. [2] F. Z. Dahmani, Y. Xiao, J. Zhang, Y. Yu, J. Zhou, J. Yao, Adv. Healthcare Mater. 2021, 10, 2101501.
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http://dx.doi.org/10.1002/adhm.202200329DOI Listing
April 2022

"Drug-Carrier" Synergy Therapy for Amyloid-β Clearance and Inhibition of Tau Phosphorylation via Biomimetic Lipid Nanocomposite Assembly.

Adv Sci (Weinh) 2022 05 20;9(14):e2106072. Epub 2022 Mar 20.

Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education), State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 210009, China.

Amyloid-β (Aβ) toxicity is considered to be companioned by Tau phosphorylation in Alzheimer's disease (AD). The clinical AD therapy is usually subjected to low blood-brain barrier (BBB) penetration and complex interaction mechanisms between Aβ and phosphorylated Tau. A "Drug-Carrier" synergy therapy is herein designed to simultaneously target Aβ and Tau-associated pathways for AD treatment. To imitate natural nanoparticle configuration, the endogenous apolipoprotein A-I and its mimicking peptide 4F fused angiopep-2 (Ang) are sequentially grafted onto lipid nanocomposite (APLN), providing liberty of BBB crossing and microglia targeted Aβ clearance. For synergy treatment, methylene blue (MB) is further assembled into APLN (APLN/MB) for Tau aggregation inhibition. After intravenous administration, the optimized density (5 wt%) of Ang ligands dramatically enhances APLN/MB intracerebral shuttling and accumulation, which is 2.15-fold higher than that Ang absent-modification. The site-specific release of MB collaborates APLN to promote Aβ capture for microglia endocytosis clearance and reduce p-Tau level by 25.31% in AD pathogenesis. In AD-Aβ-Tau bearing mouse models, APLN/MB can relieve AD symptoms, rescue neuron viability and cognitive functions. Collectively, it is confirmed that "Drug-Carrier" synergy therapy of APLN/MB is a promising approach in the development of AD treatments.
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http://dx.doi.org/10.1002/advs.202106072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108666PMC
May 2022

PRMT5 regulates RNA m6A demethylation for doxorubicin sensitivity in breast cancer.

Mol Ther 2022 Jul 10;30(7):2603-2617. Epub 2022 Mar 10.

The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an 710032, China. Electronic address:

Cancer cells respond to various stressful conditions through the dynamic regulation of RNA m6A modification. Doxorubicin is a widely used chemotherapeutic drug that induces DNA damage. It is interesting to know whether cancer cells regulate the DNA damage response and doxorubicin sensitivity through RNA m6A modification. Here, we found that doxorubicin treatment significantly induced RNA m6A methylation in breast cancer cells in both a dose- and a time-dependent manner. However, protein arginine methyltransferase 5 (PRMT5) inhibited RNA m6A modification under doxorubicin treatment by enhancing the nuclear translocation of the RNA demethylase AlkB homolog 5 (ALKBH5), which was previously believed to be exclusively localized in the nucleus. Then, ALKBH5 removed the m6A methylation of BRCA1 for mRNA stabilization and further enhanced DNA repair competency to decrease doxorubicin efficacy in breast cancer cells. Importantly, we identified the approved drug tadalafil as a novel PRMT5 inhibitor that could decrease RNA m6A methylation and increase doxorubicin sensitivity in breast cancer. The strategy of targeting PRMT5 with tadalafil is a promising approach to promote breast cancer sensitivity to doxorubicin through RNA methylation regulation.
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http://dx.doi.org/10.1016/j.ymthe.2022.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263239PMC
July 2022

Lipoprotein-Inspired Nanoscavenger for the Three-Pronged Modulation of Microglia-Derived Neuroinflammation in Alzheimer's Disease Therapy.

Nano Lett 2022 03 10;22(6):2450-2460. Epub 2022 Mar 10.

Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education), State Key Laboratory of Natural Medicines, Department of Pharmaceutics, NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, China Pharmaceutical University, Nanjing 210009, China.

The inflammatory dysfunction of microglia from excess amyloid-β peptide (Aβ) disposal is an overlooked but pathogenic event in Alzheimer's disease (AD). Here, we exploit a native high-density lipoprotein (HDL)-inspired nanoscavenger (pHDL/Cur-siBACE1) that combines the trinity of phosphatidic acid-functionalized HDL (pHDL), curcumin (Cur), and β-site APP cleavage enzyme 1 targeted siRNA (siBACE1) to modulate microglial dysfunction. By mimicking the natural lipoprotein transport route, pHDL can penetrate the blood-brain barrier and sequentially target Aβ plaque, where Aβ catabolism is accelerated without microglial dysfunction. The benefit results are from a three-pronged modulation strategy, including promoted Aβ clearance with an antibody-like Aβ binding affinity, normalized microglial dysfunction by blocking the NF-κB pathway, and reduced Aβ production by gene silence (44%). After treatment, the memory deficit and neuroinflammation of APPswe/PSEN 1dE9 mice are reversed. Collectively, this study highlights the double-edged sword role of microglia and provides a promising tactic for modulating microglial dysfunction in AD treatment.
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http://dx.doi.org/10.1021/acs.nanolett.2c00191DOI Listing
March 2022

Versatile nanomaterials for Alzheimer's disease: Pathogenesis inspired disease-modifying therapy.

J Control Release 2022 05 4;345:38-61. Epub 2022 Mar 4.

Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education), State Key Laboratory of Natural Medicines, Department of Pharmaceutics, NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, China Pharmaceutical University, Nanjing 210009, China. Electronic address:

Current therapeutic strategies for Alzheimer's disease (AD) face the dilemma of no effective drugs that can delay the onset or slow the disease progression. Despite tremendous effort being involved, several anti-AD drugs come into clinical trials but with a moderate-to-poor success rate due to the complex AD pathogenesis and the blood-brain barrier (BBB). Insight into the complex AD pathogenesis is enabling new inspiration that have the potential to help improve our understanding and design of anti-AD nanomedicine. Herein, the complex AD pathogenesis and interaction between different therapeutic targets are summarized and highlighted, and key challenges facing translation of anti-AD nanomedicine from benchtop to bedside are discussed. Following combing through the complex pathogenesis and a contextual overview of clinical status of anti-AD compounds, we discuss the recent advances of exploring versatile nanomaterials in AD treatment from the pathogenesis. The focus here is especially on how to design pathogenesis-inspired nanomaterials for delivering therapeutics cross BBB and modulating the AD pathology by themselves as active ingredients. Collectively, this review highlights the pathogenesis-oriented nanomedicine design and provides with an easily accessible guide to the key opportunities and challenges currently facing the anti-AD nanomedicine.
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http://dx.doi.org/10.1016/j.jconrel.2022.02.034DOI Listing
May 2022

Lipoprotein-biomimetic nanostructure enables tumor-targeted penetration delivery for enhanced photo-gene therapy towards glioma.

Bioact Mater 2022 Jul 2;13:286-299. Epub 2021 Nov 2.

State Key Laboratory of Natural Medicines, Department of Pharmaceutics, Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China.

Glioma is one of the most malignant primary tumors affecting the brain. The efficacy of therapeutics for glioma is seriously compromised by the restriction of blood-brain barrier (BBB), interstitial tumor pressure of resistance to chemotherapy/radiation, and the inevitable damage to normal brain tissues. Inspired by the natural structure and properties of high-density lipoprotein (HDL), a tumor-penetrating lipoprotein was prepared by the fusion tLyP-1 to apolipoprotein A-I-mimicking peptides (D4F), together with indocyanine green (ICG) incorporation and lipophilic small interfering RNA targeted HIF-1α (siHIF) surface anchor for site-specific photo-gene therapy. tLyP-1 peptide is fused to HDL-surface to facilitate BBB permeability, tumor-homing capacity and -site accumulation of photosensitizer and siRNA. Upon NIR light irradiation, ICG not only served as real-time targeted imaging agent, but also provided toxic reactive oxygen species and local hyperthermia for glioma phototherapy. The HIF-1α siRNA in this nanoplatform downregulated the hypoxia-induced HIF-1α level in tumor microenvironment and enhanced the photodynamic therapy against glioma. These studies demonstrated that the nanoparticles could not only efficiently across BBB and carry the payloads to orthotopic glioma, but also modulate tumor microenvironment, thereby inhibiting tumor growth with biosafety. Overall, this study develops a new multifunctional drug delivery system for glioma theranostic, providing deeper insights into orthotopic brain tumor imaging and treatment.
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http://dx.doi.org/10.1016/j.bioactmat.2021.10.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8844848PMC
July 2022

Risk factors for recurrence after Bankart repair: a systematic review and meta-analysis.

J Orthop Surg Res 2022 Feb 20;17(1):113. Epub 2022 Feb 20.

Department of Orthopaedics, Lanzhou University Second Hospital, No. 82 Cuiyingmen, Chengguan District, Lanzhou, 730030, Gansu, China.

Background: The aim of this literature review was to identify preoperative risk factors associated with recurrent instability after Bankart repair.

Methods: The PubMed, Web of Science, Embase, and Cochrane Library databases were searched for potentially eligible articles. Two reviewers independently screened the titles and abstracts using prespecified criteria. Articles were included if they clearly stated the risk factors for recurrence after Bankart repair. Data on patient characteristics and recurrence rate were collected from each study. A random-effects model was used for the meta-analysis and the statistical analysis was performed using Review Manager 5.4 software.

Results: Nineteen studies that included 2922 participants met the inclusion criteria. The overall pooled prevalence of recurrent instability was 15.3% (range 6.9-42). The mean follow-up duration was 40.5 months (18-108). Twenty-one risk factors were identified, 10 of which were explored quantitatively. Statistically significant risk factors for recurrent instability following a Bankart procedure were age under 20 years (odds ratio [OR] 4.24, 95% confidence interval [CI] 2.8-96.23, p < 0.00001), a Hill-Sachs lesion (OR 3.61, 95% CI 2.06-6.33, p < 0.00001), a glenoid bone lesion (OR 2.8, 95% CI 1.96-4.01, p < 0.00001), shoulder hyperlaxity (OR 4.55, 95% CI 2.19-9.44, p < 0.0001), and an off-track lesion (OR 5.53, 95% CI 2.21-13.86, p = 0.0003). There was moderate evidence indicating that male sex (OR 1.6, 95% CI 1.07-2.37, p = 0.02) and playing contact sports (OR 1.54, 95% CI 0.96-2.45, p = 0.07) were further risk factors. Dominant side, a superior labrum from anterior to posterior (SLAP) lesion, and more than five preoperative dislocations were not found to be risk factors.

Conclusions: Patients younger than 20 years of age, a Hill-Sachs lesion, a glenoid bone lesion, shoulder hyperlaxity, and an off-track lesion appear to be significant predictors of recurrent instability following a Bankart procedure. Factors such as male sex and playing contact sports were associated with recurrent instability. Dominant side, a SLAP lesion, and more than five preoperative dislocations were not significant risk factors.
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http://dx.doi.org/10.1186/s13018-022-03011-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8859902PMC
February 2022

Sarcopenia as a novel prognostic factor in the patients of primary localized gastrointestinal stromal tumor.

BMC Cancer 2022 Feb 17;22(1):179. Epub 2022 Feb 17.

The First Affiliated Hospital of China Medical University, 155 Nanjing Street, Shenyang, Liaoning, China.

Background: Sarcopenia predicts poor prognosis of a variety of gastrointestinal malignancies. However, there is a lack of study on the association between skeletal muscle index (SMI) and the prognosis of gastrointestinal stromal tumor (GIST). The aim of this study is to develop a novel nomogram based on sarcopenia for GIST patients to predict overall survival (OS).

Methods: SMI was measured by computed tomography scan of 107 patients who underwent resection for primary localized gastrointestinal stromal tumor (GIST). Sarcopenia was defined by cutoff values for SMI as 40.1 cm/m and 39.8 cm/m using optimum stratification for males and females respectively. Factors were included in the nomogram were specified by univariate and multiple Cox proportional hazard analysis. Concordance index (C-index) and calibration curves were conducted to measure the discrimination and accuracy of the nomogram. The utility of the nomogram was assessed by the decision curve analysis (DCA).

Results: Twenty-eight (26.2%) of 107 patients were sarcopenic. Sarcopenia was correlated significantly with body mass index, albumin, female sex, resection style, mitotic index, rupture status, survival. Sarcopenia was significantly related to decreased overall survival (p = 0.003).The nomogram including sarcopenia status, resection style and mitotic index had an excellent discrimination with C-index 0.794. The calibration curves represented a good accordance between the actual observation and nomogram prediction for overall survival. Decision curve analysis illustrated that the nomogram was helpful in clinic.

Conclusions: We developed a nomogram based on sarcopenia to predict overall survival after resection of GISTs which is an effective and favorable prognostication tool.
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http://dx.doi.org/10.1186/s12885-022-09278-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8851766PMC
February 2022

Nanomedicine potentiates mild photothermal therapy for tumor ablation.

Asian J Pharm Sci 2021 Nov 15;16(6):738-761. Epub 2021 Oct 15.

Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education), State Key Laboratory of Natural Medicines, NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.

The booming photothermal therapy (PTT) has achieved great progress in non-invasive oncotherapy, and paves a novel way for clinical oncotherapy. Of note, mild temperature PTT (mPTT) of 42-45 °C could avoid treatment bottleneck of the traditional PTT, including nonspecific injury to normal tissues, vasculature and host antitumor immunity. However, cancer cells can resist mPTT via heat shock response and autophagy, thus leading to insufficient mPTT monotherapy to ablate tumor. To overcome the deficient antitumor efficacy caused by thermo-resistance of cancer cells and mono mPTT, synergistic therapies towards cancer cells have been conducted with mPTT. This review summarizes the recent advances in nanomedicine-potentiated mPTT for cancer treatment, including strategies for enhanced single-mode mPTT and mPTT plus synergistic therapies. Moreover, challenges and prospects for clinical translation of nanomedicine-potentiated mPTT are discussed.
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http://dx.doi.org/10.1016/j.ajps.2021.10.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8739255PMC
November 2021

Retracted: Dynamic Evaluation of Orthodontically-Induced Tooth Movement, Root Resorption, and Alveolar Bone Remodeling in Rats by in Vivo Micro-Computed Tomography.

Med Sci Monit 2021 12 17;27:e935851. Epub 2021 Dec 17.

Department of Orthodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, China (mainland).

This publication has been retracted by the Editor due to the identification of non-original figure images and manuscript content that raise concerns regarding the credibility and originality of the study and the manuscript. Reference: Jianping Zhou, Fengxue Yang, Xiaolin Xu, Gang Feng, Jun Chen, Jinglin Song, Hongwei Dai. Dynamic Evaluation of Orthodontically-Induced Tooth Movement, Root Resorption, and Alveolar Bone Remodeling in Rats by in Vivo Micro-Computed Tomography. Med Sci Monit, 2018; 24: 8306-8314. DOI: 10.12659/MSM.912470.
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http://dx.doi.org/10.12659/MSM.935851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8690043PMC
December 2021

Corrigendum: CircHIPK3 Promotes Metastasis of Gastric Cancer miR-653-5p/miR-338-3p-NRP1 Axis Under a Long-Term Hypoxic Microenvironment.

Front Oncol 2021 12;11:783320. Epub 2021 Nov 12.

Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.

[This corrects the article DOI: 10.3389/fonc.2020.01612.].
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http://dx.doi.org/10.3389/fonc.2021.783320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8633827PMC
November 2021

Influence of ligand geometry on cholinesterase enzyme - A comparison of 1-isoindolinone based structural analog with Donepezil.

J Mol Struct 2022 Jan 31;1247. Epub 2021 Aug 31.

Drug Discovery Program, KCVA Medical Center, Midwest Veterans' Biomedical Research Foundation, 4801 E. Linwood Blvd., Kansas City, MO 64128, United States.

Donepezil (DNPZ) is one of the few FDA-approved widely used medication in the clinical care of Alzheimer's disease (AD) patients. To investigate the effect of geometry and to find the significance of an enol form if any in DNPZ on acetylcholinesterase (AChE) inhibition, we changed the tetrahedral geometry of DNPZ to planar trigonal pyramidal geometry by replacing the α-carbon atom next to ketone functionality with a nitrogen atom. To mimic 1-indanone in DNPZ, we selected 1-isoindolinone framework to synthesize 25 new DNPZ derivatives and characterized using H NMR, C NMR and ESI-MS spectroscopy methods. Drug likeliness profile for each compound was predicted using Molinspiration online software following Lipinski's rule. Commercially available assay kits were used to measure AChE and butyrylcholinesterase (BuChE) inhibitory effects. NIH/3T3 mouse embryonic fibroblast cell line was used to measure cytotoxic and proliferation effects using LDH and MTT assay, respectively. Compound #20 was selected for comparative computational docking, modelling and physicochemical studies. Our results show that DNPZ with tetrahedral geometry has 3-fold higher AChE inhibition as compared to compound #20 with planar trigonal pyramidal geometry. Our approach may be useful as a novel indirect method to study the significance of the enol form in DNPZ (or similar compounds), since constant interconversion between the keto and enol forms does not permit a direct determination of the effect of the enol form of DNPZ . Overall, we conclude that the tetrahedral is a better fit and any change in geometry significantly drives down the cholinesterase inhibitory effect of DNPZ.
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http://dx.doi.org/10.1016/j.molstruc.2021.131385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8589283PMC
January 2022
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