Publications by authors named "Haijun Chen"

129 Publications

Isochromanoindolenines suppress triple-negative breast cancer cell proliferation partially via inhibiting Akt activation.

Int J Biol Sci 2021 2;17(4):986-994. Epub 2021 Mar 2.

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.

As the most malignant subtype of breast cancers, triple-negative breast cancer (TNBC) lacks effective targeted therapeutics clinically to date. In this study, one lead compound FZU-0025-065 with isochromanoindolenine scaffold was identified by a cell-based screening. Among nine breast cancer cell lines tested, TNBC are the most sensitive cell lines to FZU-0025-065. FZU-0025-065 inhibits TNBC cell growth in a time- and dosage-dependent manner. FZU-0025-065 suppresses the expression of cell cycle dependent kinase 4 (CDK4), Cyclin D1 and Cyclin B1; meanwhile, elevates the expression of cell cycle dependent kinase inhibitor p21 and p27. Importantly, we found that FZU-0025-065 suppresses AKT activation in a time- and dosage-dependent manner. Over-expression of constitutive active AKT partially rescues FZU-0025-065 induced cell growth inhibition in MDA-MB-468 cells, indicating FZU-0025-065 suppresses TNBC cell growth partially via inhibiting AKT activation. Finally, FZU-0025-065 suppresses TNBC cell growth in a xenograft mouse model. Taken together, our findings suggested that isochromanoindolenine derivative FZU-0025-065 inhibits TNBC via suppressing the AKT signaling and that FZU-0025-065 may be useful for TNBC treatment.
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http://dx.doi.org/10.7150/ijbs.48170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040301PMC
March 2021

Deployment of a bioabsorbable plate as the rigid buttress for skull base repair after endoscopic pituitary surgery.

Gland Surg 2021 Mar;10(3):1010-1017

Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, China.

Background: Bioresorbable alloplastic implants have become desirable as a rigid buttress for reconstructing skull base defects. This study aimed to describe the use of a biodegradable plate (PolyMax RAPID) in skull base repair of endoscopic endonasal pituitary surgery and to investigate the clinical outcome and safety of this novel method.

Methods: Between January 2019 and January 2020, 22 patients with pituitary adenomas who underwent endoscopic skull base repair with a Polymax RAPID plate were included. After endonasal transsphenoidal surgery, a trimmed bioresorbable plate was placed in the position between the dura and the bone of the skull base to reconstruct the sellar floor and buttress the pituitary gland and sellar packing. The patient demographics, radiologic imaging, and postoperative outcomes were carefully reviewed. All patients were followed up by a routine nasal endoscopic assessment and radiologic examinations.

Results: The present study comprised 10 (45.5%) males and 12 (54.4%) females with an average age of 51.9 years. There were 7 (31.8%) growth hormone (GH) secreting adenomas, 2 (9.1%) thyroid stimulating hormone (TSH) secreting adenomas, and 13 (59.1%) non-functioning adenomas. Enlarged sellar floor and paranasal sinusitis were seen in 13 (59.1%) and 11 (50.0%) cases shown by preoperative computed tomography (CT) or magnetic resonance imaging (MRI), respectively. There were 6 (27.3%) grade-1 and 16 (72.7%) grade-0 cases by intraoperative cerebrospinal fluid (CSF) leak grading. None of these patients received lumbar drains postoperatively and no postoperative CSF rhinorrhea was detected in our series. The PolyMax RAPID plates which could be clearly identified on postoperative CT or sagittal T1-weighted MRI were shown to provide an ideal rigid buttress for sellar repair.

Conclusions: The Polymax RAPID plate can be an optimal implant to achieve rigid repair of sellar floor defects after endonasal transsphenoidal pituitary surgery.
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http://dx.doi.org/10.21037/gs-20-642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033064PMC
March 2021

MiR-21-5p Induces Pyroptosis in Colorectal Cancer TGFBI.

Front Oncol 2020 5;10:610545. Epub 2021 Feb 5.

Department of Oncology, Kunshan Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Kunshan, China.

Pyroptosis is a distinct form of programmed cell death in eukaryotic cells that has garnered increasing attention in cancer-related research. Moreover, although miR-21 has been reported as abnormally expressed in colorectal cancer, due to a lack of in-depth research on the transcriptional regulation mechanisms of miR-21, its clinical usage remains limited. Our study is the first, to our knowledge, to compare the clinical manifestations and laboratory phenotypes associated with miR-21-3p and miR-21-5p. Morphologically, the transfection of miR-21-3p or miR-21-5p inhibitors, as well as miR-21-5p mimics into HCT-116 and HT-29 cell lines, induced cell death. Surprisingly, overexpression of miR-21-5p induced cell death more strongly than its knockdown. Mechanistic studies of miR-21-5p overexpression revealed that various inflammatory factors including IL-1β and IL-18 were released, while pyroptosis-associated mRNAs were upregulated and proteins were activated. Moreover, miR-21-5p was found to act as a downstream factor to significantly and directly regulate transforming growth factor beta-induced (. Specifically, miR-21-5p overexpression caused downregulation of , which may have led to pyroptosis. Collectively, we revealed that miR-21-5p induces pyroptosis in colorectal cancer regulation, thereby providing important mechanistic insights into its antitumor effects and expanding its potential for clinical applications.
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http://dx.doi.org/10.3389/fonc.2020.610545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892456PMC
February 2021

Transmission electron microscopy sample preparation method for micrometer-sized powder particles using focused ion beam.

Micron 2021 Apr 5;143:103030. Epub 2021 Feb 5.

Vacuum Interconnected Nanotech Workstation (Nano-X), Suzhou Institute of Nano-Tech and Nano-Bionics (SINANO), Chinese Academy of Sciences (CAS), Suzhou, 215123, China. Electronic address:

A TEM sample preparation technique for micrometer-sized powder particles in the 1-10 μm size range is proposed, using a focused ion beam (FIB) system. It is useful for characterizing elemental distributions across an entire cross-section of a particle. It is a simple and universal method without using any embedding agent, enabling the powder particles with different size, shape or orientation to be easily selected based on the SEM observations. The suitable particle is covered with Pt coating layers through an ion-beam-assisted deposition. The Pt coating layers provide sufficient support for the TEM lamella. A small piece of tungsten needle is used as a support under the particle by taking a series of operations using a micromanipulator. The particle can be precisely thinned by the ion beam to be suitable for both TEM observation and EDX elemental mapping. This novel technique reduces the TEM sample preparation time to a few hours, allowing much higher efficiency compared to complicated and time-consuming embedding methods.
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http://dx.doi.org/10.1016/j.micron.2021.103030DOI Listing
April 2021

Constructing MoS/Lignin-derived carbon nanocomposites for highly efficient removal of Cr(VI) from aqueous environment.

J Hazard Mater 2021 Apr 14;408:124847. Epub 2020 Dec 14.

State Key Laboratory of Nuclear Resources and Environment, East China University of Technology, Nanchang, Jiangxi 330013, China.

Effective removal of Cr(VI) pollution from aquatic environment is in pressing need because of the detrimental effect of Cr(VI) to human health. Herein, we report a facile two-step approach to synthesis MoS/Lignin-derived Carbon (MoS@LDC) nanocomposites for highly efficient elimination of Cr(VI) from aqueous solutions. The MoS@LDC exhibited outstanding removal efficient for Cr(VI) (198.70 mg/g at pH = 2.0, T = 298.15 K and C = 20.0 mg/L). 99.35% of Cr(VI) can be removed by the composites in 30 min. Thermodynamic and kinetic studies suggest the removal of Cr(VI) is through both adsorption and reduction. The performance of MoS@LDC can be further enhanced by hydrogen plasma treatments, which was attributed to the sulfur vacancies induced improvement in the reduction activity of MoS layer. The results of this work can guide the rational design of high-performance nanocomposite for efficient remediation of heavy metals in aquatic environment.
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http://dx.doi.org/10.1016/j.jhazmat.2020.124847DOI Listing
April 2021

Effect of early use of ivabradine on left ventricular remodeling after primary percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction: A pilot test.

Ann Noninvasive Electrocardiol 2021 03 24;26(2):e12816. Epub 2020 Dec 24.

Department of Cardiology, Fuwai Hospital Chinese Academy of Medical Sciences, Shenzhen, China.

Objective: To investigate the effect of early use of ivabradine on left ventricular remodeling after primary percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI).

Methods: A total of 66 STEMI patients with sinus rhythm and the resting heart rate ≥80 bpm after successful emergency PCI were included. The patients in the test group were treated with ivabradine combined with metoprolol at 12 hr after PCI, while the control group was given only metoprolol orally. Their resting heart rate was controlled to <70 bpm at discharge and followed for 180 days. Heart rate and blood pressure were measured regularly. Echocardiogram was performed. N-terminal pro-B-type natriuretic peptide (NT-proBNP), high sensitivity troponin T, high sensitivity troponin I, and high sensitivity C-reactive protein were measured. The major adverse cardiovascular events during hospitalization and follow-up period were recorded.

Results: Compared with the control group, the heart rate of the test group decreased significantly (p < .05). Compared with the control group, the left ventricular end-diastolic volume and left ventricular end-systolic volume were significantly decreased while left ventricular ejection fraction was significantly increased in the test group at 90 days after operation. NT-proBNP of the test group was significantly lower than that of the control group at 7 days after operation (p < .05).

Conclusion: For STEMI patients, early use of ivabradine combined with standard therapy such as β-blocker after successful reperfusion can achieve effective heart rate control, with great safety and tolerance. But the effect of ivabradine on left ventricular remodeling is uncertain.
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http://dx.doi.org/10.1111/anec.12816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935096PMC
March 2021

A Hydrogen-Initiated Chemical Epitaxial Growth Strategy for In-Plane Heterostructured Photocatalyst.

ACS Nano 2020 Nov 25. Epub 2020 Nov 25.

School of Engineering, Edith Cowan University, 270 Joondalup Drive, Joondalup, Western Australia 6027, Australia.

Integrating carbon nitride with graphene into a lateral heterojunction would avoid energy loss within the interlaminar space region on conventional composites. To date, its synthesis process is limited to the bottom-up method which lacks the targeting and homogeneity. Herein, we proposed a hydrogen-initiated chemical epitaxial growth strategy at a relatively low temperature for the fabrication of graphene/carbon nitride in-plane heterostructure. Theoretical and experimental analysis proved that methane via generation from the hydrogenated decomposition of carbon nitride triggered the graphene growth along the active sites at the edges of confined spaces. With the enhanced electrical field from the deposited graphene (0.5%), the performances on selective photo-oxidation and photocatalytic water splitting were promoted by 5.5 and 3.7 times, respectively. Meanwhile, a 7720 μmol/h/g hydrogen evolution rate was acquired without any cocatalysts. This study provides an top-down strategy to synthesize in-plane catalyst for the utilization of solar energy.
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http://dx.doi.org/10.1021/acsnano.0c07934DOI Listing
November 2020

Diverse Functionalization of Tetrahydro-β-carbolines or Tetrahydro-γ-carbolines via Oxidative Coupling Rearrangement.

J Org Chem 2021 01 24;86(1):794-812. Epub 2020 Nov 24.

College of Chemistry, Fuzhou University, Fuzhou, Fujian 350116, China.

We report herein diverse functionalization of tetrahydro-β-carbolines (THβCs) or tetrahydro-γ-carbolines (THγCs) via oxidative coupling rearrangement. The treatment of THβCs or THγCs with -BuOOH (TBHP) afforded 3-peroxyindolenines, followed by HCl catalyzed indolation to form unexpected 2-indolyl-3-peroxyindolenines. Further rearrangement of these peroxides allows for rapid access to a skeletally diverse chemical library in good to excellent yields.
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http://dx.doi.org/10.1021/acs.joc.0c02351DOI Listing
January 2021

Long noncoding RNA H19 act as a competing endogenous RNA of Let-7g to facilitate IEC-6 cell migration and proliferation via regulating EGF.

J Cell Physiol 2021 Apr 23;236(4):2881-2892. Epub 2020 Nov 23.

Department of Burn Surgery, The Affiliated Huaihai Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.

Intestinal mucosal injury is one of the most significant complications of burns. In our previous study, it was found that autophagy could alleviate burn-induced intestinal injury, but the underlying mechanisms are still unclear. Irregular expression of long noncoding RNAs (lncRNAs) is present in many diseases, including burns. However, the relationship between lncRNAs and intestinal mucosal injury requires further elucidation. In this study, we established a burn mice model and detected the expression level of autophagy-related proteins. Then, H19 content after autophagy intervention was tested in vitro and in vivo. The interaction of H19 with Let-7g and that of Let-7g with epidermal growth factor (EGF) were verified by dual-luciferase reporter assays. We found that the expression of the autophagy-associated proteins LC3-II and Beclin-1 was raised in the intestinal tract of the burn mice model. Similarly, the transfection of H19 raised autophagy levels. H19 was elevated after autophagy intervention in vitro and in vivo. H19 overexpression was able to promote IEC-6 cell migration and proliferation. Let-7g was suppressed by the overexpression of H19 and the combination of Let-7g mimic was able to abolish the physiological effect of H19. Moreover, the suppression of Let-7g increased the expression of EGF protein, which heightened IEC-6 cell migration and proliferation. Besides this, dual-luciferase assays revealed that Let-7g was a direct target of H19 as well as the EGF gene. Taken together, autophagy-mediated H19 increases in mouse intestinal tract after severe burn and functions as a sponge to Let-7g to regulate EGF, which suggests that H19 serves as a potential therapeutic target and biomarker for intestinal mucosal injury after burns.
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http://dx.doi.org/10.1002/jcp.30061DOI Listing
April 2021

Long-term outcomes in Chinese patients with chronic hepatitis B receiving nucleoside/nucleotide analogue therapy in real-world clinical practice: 5-year results from the EVOLVE study.

Antivir Ther 2020 ;25(6):293-304

Bristol-Myers Squibb, Shanghai, China.

Background: In China, the optimal management of individuals living with chronic HBV infection (CHB) remains an unmet need. The EVOLVE Study was a 5-year prospective, longitudinal, observational study that compared the clinical outcomes in treatment-naive CHB patients receiving entecavir (ETV) or lamivudine (LAM)-based therapies.

Methods: Males or females aged ≥18 years, diagnosed with CHB regardless of cirrhosis or hepatitis B e antigen (HBeAg) status were enrolled from tier 2 city hospitals (between 2012-2014). The choice of initial therapy and subsequent treatment modifications was at the discretion of treating physicians. Key outcomes included treatment modifications, virological response (HBV DNA <300 copies/ml) and HBV disease progression.

Results: Of the 3,408 patients enrolled, 1,807 and 628 received ETV and LAM-based therapy, respectively. The mean age was 39.5 years, 74% were male and 22.9% had cirrhosis. The rate of treatment modification was higher in the LAM-based versus ETV group (25.9% versus 13.7%); viral breakthrough was the most common reason in the LAM-based group versus financial reasons in the ETV group. At week 240, the virological response rate was 73% in both treatment groups. Compared with LAM-based therapy, ETV was associated with a significantly lower incidence of viral breakthrough (12.6% versus 2.1%) and genotypic resistance (10.1% versus 1.2%; P<0.0001 for both); significantly lower risk of HBV disease progression (14.0% versus 10.7%; P=0.0113); and lower rates of progression to decompensated cirrhosis (9.6% versus 6.4%) and hepatocellular carcinoma (1.9% versus 0.8%).

Conclusions: This real-world, longitudinal study demonstrated a significantly lower risk of HBV-related disease progression, viral breakthrough and resistance with ETV versus LAM-based therapy. ClinicalTrials.gov NCT01726439.
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http://dx.doi.org/10.3851/IMP3372DOI Listing
January 2020

Synthesis and structure-activity relationship studies of LLY-507 analogues as SMYD2 inhibitors.

Bioorg Med Chem Lett 2020 11 2;30(22):127598. Epub 2020 Oct 2.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China; University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing 100049, China. Electronic address:

SET and MYND domain-containing protein 2 (SMYD2), a lysine methyltransferase, is reported to catalyze the methylation of lysine residues on histone and non-histone proteins. As a potential target for cancer therapy, there are several SMYD2 inhibitors are reported, LLY-507 as a cell-active inhibitor exhibits submicromolar potency against SMYD2 in several cancer cell lines. To know which structural fragment of LLY-507 is suitable for chemical modification, three sites are chosen for structure-activity relationship studies (SARs). Among our focused library, compounds 43 and 44 with amide link on site C showed reasonably improved potency indicating that modification on this fragment is more flexible and introduction of electrophilic warheads in this position might provide lysine-targeting covalent inhibitors for SMYD2.
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http://dx.doi.org/10.1016/j.bmcl.2020.127598DOI Listing
November 2020

Glioblastoma Therapy Using Codelivery of Cisplatin and Glutathione Peroxidase Targeting siRNA from Iron Oxide Nanoparticles.

ACS Appl Mater Interfaces 2020 Sep 17;12(39):43408-43421. Epub 2020 Sep 17.

Department of Neurosurgery, Qilu Hospital and Institute of Brain and Brain-Inspired Science, Cheeloo College of Medicine, Shandong University, 107 Wenhua Xi Road, Jinan, Shandong 250012, P. R. China.

Glioblastoma (GBM) is the most common and lethal type of malignant brain tumor in adults. Currently, interventions are lacking, the median overall survival of patients with GBM is less than 15 months, and the postoperative recurrence rate is greater than 60%. We proposed an innovative local chemotherapy involving the construction of gene therapy-based iron oxide nanoparticles (IONPs) as a treatment for patients with glioblastoma after surgery that targeted ferroptosis and apoptosis to address these problems. The porous structure of IONPs with attached carboxyl groups was modified for the codelivery of small interfering RNA (siRNA) targeting glutathione peroxidase 4 (si-GPX4) and cisplatin (Pt) with high drug loading efficiencies. The synthesized folate (FA)/Pt-si-GPX4@IONPs exerted substantial effects on glioblastoma in U87MG and P3#GBM cells, but limited effects on normal human astrocytes (NHAs). During intracellular degradation, IONPs significantly increased iron (Fe and Fe) levels, while Pt destroyed nuclear DNA and mitochondrial DNA, leading to apoptosis. Furthermore, IONPs increased HO levels by activating reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX). The Fenton reaction between Fe, Fe, and intracellular HO generated potent reactive oxygen species (ROS) to initiate ferroptosis, while the co-released si-GPX4 inhibited GPX4 expression and synergistically improved the therapeutic efficacy through a mechanism related to ferroptosis. As a result, superior therapeutic effects with low systemic toxicity were achieved both and , indicating that our nanoformulations might represent safe and efficient ferroptosis and apoptosis inducers for use in combinatorial glioblastoma therapy.
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http://dx.doi.org/10.1021/acsami.0c12042DOI Listing
September 2020

Experimental investigation of the dynamic cavitation behavior and wall static pressure characteristics through convergence-divergence venturis with various divergence angles.

Sci Rep 2020 Aug 25;10(1):14172. Epub 2020 Aug 25.

School of Energy and Power Engineering, Xi'an Jiaotong University, Xi'an, 710049, China.

As a highly efficient and energy-saving cavitation method, Venturi cavitation is widely used in many industrial fields. This study synchronously investigated the cavity behavior and its corresponding wall static pressure characteristics in Venturi channels with various divergence angles to research the role of the divergence angle in cavity shape and the wall static pressure oscillation. Five rectangular Venturi channels with different divergence angles (4°, 6°, 8°, 10°, and 12°) were tested at the cavitation number (0.3-1.0). Based on the dynamic behaviour of gas-liquid interface, three cavity shedding types were identified: front shedding (I), central shedding (II) and tail shedding (III). A modified correlation for predicting average cavity length was proposed with the consideration of the effect of the divergence angle. Combined with the wall static pressure characteristics, as the divergence angle increased, the wall static pressure fluctuation in the Venturi became more intense. According to the wall static pressure oscillation characteristics, for the larger divergence angles (θ = 6°, 8°, 10° and 12°), the wall static pressure oscillation frequency was the same as the cavity shedding frequency and increased with the increase of the divergence angle. For smaller divergence angle (θ = 4°), no definite periodicity in pressure oscillation frequency could be observed.
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http://dx.doi.org/10.1038/s41598-020-68317-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447808PMC
August 2020

Electrospun composite nanofibers with all-trans retinoic acid and MWCNTs-OH against cancer stem cells.

Life Sci 2020 Oct 28;258:118152. Epub 2020 Jul 28.

Department of Neurosurgery, Qilu Hospital, Shandong University, Jinan, Shandong, China. Electronic address:

Aims: Cancer stem cells (CSCs) are the source of tumors and play a key role in the resistance of cancer to therapies. To improve the current therapies against CSCs, in this work we developed a novel system of electrospun polycaprolactone (PCL) nanofibers containing hydroxylated multi-walled carbon nanotubes (MWCNTs-OH) and all-trans retinoic acid (ATRA).

Materials And Methods: The nanofiber membranes were forged by electrospinning, and the physical and chemical properties of the nanofiber membranes were evaluated by scanning electron microscopy, XRD and Raman etc. The photothermal properties of nanofiber membranes and their effects on CSCs differentiation and cytotoxicity were investigated. Finally, the anti-tumor effect of nanofiber membranes in vivo was evaluated.

Key Findings: The nanofibers formed under optimal conditions were smooth without beads. The nanofibrous membranes with MWCNTs-OH could increase temperature of the medium under near-infrared (NIR) illumination to suppress the viability of glioma stem cells (GSCs). Meanwhile, the added ATRA could further induce the differentiation of GSCs to destroy their stemness and reduce their resistance to heat treatment. Compared with no NIR irradiation, after 2min NIR irradiation, the membranes reduced the in-vitro viability of GSCs by 13.41%, 14.83%, and 26.71% after 1, 2, and 3 days, respectively. After 3 min daily illumination for 3 days, the viability of GSCs was only 22.75%, and similar results were observed in vivo.

Significance: These results showed efficiently cytotoxicity to CSCs by combining heat therapy and differentiation therapy. The nanofiber membranes if inserted at the site after surgical tumor removal, may hinder tumor recurrence.
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http://dx.doi.org/10.1016/j.lfs.2020.118152DOI Listing
October 2020

Increased risk of Ventriculostomy-Associated hemorrhage in patients treated with antiplatelet agents for stent-assisted coiling of ruptured intracranial aneurysms.

Br J Neurosurg 2021 Jun 9;35(3):270-274. Epub 2020 Jul 9.

Department of Neurosurgery, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.

Purpose: The aim of this study is to evaluate the impact of antiplatelet agents for stent-assisted coiling, including intravenous (IV) tirofiban as an antiplatelet premedication, on rates of external ventricular drain (EVD)-related hemorrhage in acutely ruptured intracranial aneurysms. The impact of IV tirofiban in particular was also evaluated.

Methods: Rates of radiographically identified hemorrhage associated with EVD placement were compared between patients who received an antiplatelet agent for stent-assisted coil embolization (SACE), and patients who did not receive an antiplatelet agent between June 2013 and June 2019.

Results: 78 patients treated for a ruptured aneurysm which required an EVD were included. A total of 46 patients who underwent stent-assisted coiling and received IV tirofiban and oral asipirin and clopidogrel (DAPT) were included in the antiplatelet group, while 32 who underwent single coiling and received no antiplatelet therapy were included in the control group. Overall, EVD-related hemorrhage occurred in 13 patients (16.67%): 11 (23.91%) in the antiplatelet group and 2 (6.25%) in the control group ( = 0.040). Of 37 patients who underwent computed tomography after SACE, but before the use of DAPT, 8 (21.62%) exhibited EVD-related hemorrhage after IV tirofiban therapy ( = 0.070 vs. control group). EVD-related hemorrhage was not significantly different between patients with EVD placement after coil embolization versus before coil embolization ( = 0.124). In the subgroup analysis for the antiplatelet group, we did not observed increased EVD-related hemorrhage in patients receiving EVD placement after administration of antiplatelet agents (8/27 [29.63%]) versus before administration of antiplatelet agents (3/19 [15.79%]).

Conclusion: Patients with ruptured aneurysm who receive an antiplatelet agent for stent-assisted coiling are at a higher risk for EVD-related hemorrhage. The order of EVD placement and EVT, as well as the order of EVD placement and antiplatelet initiation do not appear to be significantly different regarding the outcome of EVD-related hemorrhage.HighlightsPatients with ruptured aneurysm who receive an antiplatelet agent for stent-assisted coiling are at a higher risk for EVD-related hemorrhage.There was a trend towards higher EVD related haemorrhage when tirofiban was used but it did not reach statisitical significance.The order of EVD-whether before vs after endovascular treatment, or before vs after antiplatelet therapy did not influence the EVD-related hemorrhage rates.
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http://dx.doi.org/10.1080/02688697.2020.1787338DOI Listing
June 2021

Heterogeneous activation of peroxymonosulfate by hierarchically porous cobalt/iron bimetallic oxide nanosheets for degradation of phenol solutions.

Chemosphere 2020 Oct 22;256:127160. Epub 2020 May 22.

School of Engineering, Edith Cowan University, Joondalup, WA, 6027, Australia. Electronic address:

Bimetallic oxide nanomaterials have received much attention owing to their competing performances in heterogeneous catalysis. Herein, hierarchically porous cobalt-iron oxide nanosheets were successfully prepared using NaBH as a reductant and high concentration cetyl trimethylammonium bromide (CTAB) as a surfactant. Characterization results showed that the CTAB would induce the form of a bilayer structure while NaBH would promote the generation of enriched oxygen vacancies. As a result, the as-prepared CoFe-300 exhibited high activity for activating peroxymonosulfate and achieved 100% phenol degradation within 30 min. This excellent catalytic activity can be attributed to its hierarchically porous structure, more active sites and oxygen vacancies. Co leaching test indicated that the CoFe-300 exhibited excellent catalytic stability. Mechanistic studies suggested that two main degradation pathways were involved during phenol oxidation process, in which SO played a significant role. This work may offer a novel strategy for the synthesis of high activity catalysts and a promising system for the remediation of environmental pollutant.
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http://dx.doi.org/10.1016/j.chemosphere.2020.127160DOI Listing
October 2020

Pyrrolo [3,4-]-quinolin-9-amine compound FZU-0038-056 suppresses triple-negative breast cancer partially through inhibiting the expression of Bcl-2.

Aging (Albany NY) 2020 05 23;12(10):9621-9632. Epub 2020 May 23.

Department of Pathology, First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China.

Triple-negative breast cancer (TNBC) has a poorer prognosis than other subtypes of breast cancer; however, it lacks effective targeted therapies clinically. In this study, we found FZU-0038-056, a novel compound derived from last-stage functionalization of tetrahydro-β-carboline scaffold, showed the most potent anti-cancer activity against TNBC cells among the 42 synthesized derivatives. We found FZU-0038-056 significantly induces apoptosis in HCC1806 and HCC1937 TNBC cells. FZU-0038-056 reduces the expression levels of several anti-apoptosis proteins, including Bcl-2, Mcl-1 and XIAP. Furthermore, we found FZU-0038-056 induces apoptosis partially through inhibiting the expression of Bcl-2. Finally, we found FZU-0038-056 significantly suppresses HCC1806 xenograft tumor growth in nude mice without affecting their body weight. Therefore, FZU-0038-056 has the potential to be a new anticancer agent for treating human TNBC.
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http://dx.doi.org/10.18632/aging.103232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288966PMC
May 2020

[Roles of multidisciplinary team in diagnosis and treatment of suspected cases of COVID-19].

Zhejiang Da Xue Xue Bao Yi Xue Ban 2020 May;49(2):209-214

Department of Critical Care Medicine, Jinhua Municipal Central Hospital, Jinhua 321000, Zhejiang Province, China.

Objective: To analyze the roles of multidisciplinary team (MDT) in the diagnosis and treatment of suspected cases of coronavirus disease 2019 (COVID-19).

Methods: The clinical data of 48 patients with suspected COVID-19 admitted in Jinhua Municipal Central Hospital from January 21, 2020 to March 20, 2020 were retrospectively analyzed.

Results: In the 48 suspected cases, 18 were diagnosed with COVID-19, and 30 were excluded. Each of the confirmed cases were discussed among MDT for 2 to 12 times with an average of (4.7±3.2) times; while for non-COVID-19 patients were discussed for 2 to 4 times with an average of (2.3±0.6) times. With the guidance of MDT, one COVID-19 patient was transferred to designated provincial hospital after effective treatment; one patient complicated with acute cholecystitis underwent gallbladder puncture and drainage; and COVID-19 was excluded in a highly suspected patient after alveolar lavage fluid examination. Except one transferred patient, all 17 confirmed COVID-19 patients were cured and discharged. There was no cross-infection occurred in suspected patients during the hospitalization. There were no deaths and no medical staff infections.

Conclusions: The efficiency of diagnosis and treatment for suspected COVID-19 patients can be improved with MDT, particularly for complicated cases.
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http://dx.doi.org/10.3785/j.issn.1008-9292.2020.03.15DOI Listing
May 2020

Epidermal growth factor regulation by autophagy-mediated lncRNA H19 in murine intestinal tract after severe burn.

J Cell Mol Med 2020 05 16;24(10):5878-5887. Epub 2020 Apr 16.

Department of Burn Surgery, The Affiliated Huaihai Hospital of Xuzhou Medical University, Xuzhou, China.

To investigate the regulation of epidermal growth factor (EGF) by autophagy-mediated long non-coding RNA (lncRNA) H19 in the intestinal tracts of severely burned mice. C57BL/6J mice received third-degree burns to 30% of the total body surface area. Rapamycin and 3-methyladenine (3-MA) were used to activate and inhibit autophagy, and the changes in LC3 and Beclin1 levels were assessed by Western blotting. The effect of autophagy on lncRNA H19 was detected by qRT-PCR. Adenovirus-mediated overexpression of lncRNA H19 in IEC-6 cells was used to assess the effects of lncRNA H19 on EGF and let-7g via bioinformatics analysis, Western blotting and qRT-PCR. let-7g mimic/inhibitor was used to overexpress/inhibit let-7g, and qRT-PCR and Western blotting were used to detect the effects of let-7g on EGF. The expression levels of LC3-II, Beclin1 and lncRNA H19 were increased in intestinal tissues and IEC-6 cells after rapamycin treatment but were reversed after 3-MA treatment. LC3-II, Beclin1 and lncRNA H19 levels increased in intestinal tissues after the burn, and these increases were more significant after rapamycin treatment but decreased after 3-MA treatment. The lncRNA H19 overexpression in IEC-6 cells resulted in increased and decreased expression levels of EGF and let-7g, respectively. Furthermore, overexpression and inhibition of let-7g resulted in decreased and increased expression of EGF, respectively. Taken together, intestinal autophagy is activated after a serious burn, which can increase the transcription level of lncRNA H19. lncRNA H19 may regulate the repair of EGF via let-7g following intestinal mucosa injury after a burn.
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http://dx.doi.org/10.1111/jcmm.15262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214185PMC
May 2020

Ideal two-dimensional solid electrolytes for fast ion transport: metal trihalides MX with intrinsic atomic pores.

Nanoscale 2020 Apr;12(13):7188-7195

Department of Electronic Science and Engineering, Key Laboratory of Photo-Electronic Thin Film Device and Technology of Tianjin, Nankai University, Tianjin, 300350, China.

Exploring ultrathin two-dimensional (2D) solid electrolytes with fast ion transport is highly desirable in nanoelectronics, ionic devices and various energy storage systems, following the rapid scaling of devices to the nanometer scale. Herein, two-dimensional (2D) metal trihalides MX3 (ScCl3, ScBr3, AsI3, ScI3, YBr3, SbI3, YI3 and BiI3) with intrinsic atomic pore structures have been examined and found to be promising as realistic 2D solid electrolytes. Through examining the binding interactions and the diffusion barriers of monolayer MX3-ion (Li+, Na+, K+, Mg2+, and Ca2+) systems by utilizing first principles calculations, it is found that MX3-ion complexes are energetically favorable and the energy barriers of some MX3-ion systems are comparable to or even smaller than those of the conventional solid electrolyte systems. More significantly, the short diffusion time of Na+ and K+ ions in some monolayers MX3 at the nanosecond (ns) or even at the sub-ns scale indicates fast ion transport. In terms of practical applications, ultrafast Li+ travelling in the timescale of sub-ns to ns and Na+ in several tens ns in few-layer MX3 is achieved. In addition, the insulating nature of wide band gaps for MX3 is maintained during the ion transport, which is essential for solid electrolytes. These theoretical results provide fundamental guidance that MX3 materials with natural atomic pores are realistic candidates for 2D solid electrolytes with broad applications in ionic devices and energy storage devices.
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http://dx.doi.org/10.1039/c9nr08719bDOI Listing
April 2020

Potential sphingosine-1-phosphate-related therapeutic targets in the treatment of cerebral ischemia reperfusion injury.

Life Sci 2020 May 10;249:117542. Epub 2020 Mar 10.

Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Key Laboratory of Brain Functional Remodeling, Shandong, 107# Wenhua Xi Road, Jinan 250012, China. Electronic address:

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that regulates lymphocyte trafficking, glial cell activation, vasoconstriction, endothelial barrier function, and neuronal death pathways in the brain. Research has increasingly implicated S1P in the pathology of cerebral ischemia reperfusion (IR) injury. As a high-affinity agonist of S1P receptor, fingolimod exhibits excellent neuroprotective effects against ischemic challenge both in vivo and in vitro. By summarizing recent progress on how S1P participates in the development of brain IR injury, this review identifies potential therapeutic targets for the treatment of brain IR injury.
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http://dx.doi.org/10.1016/j.lfs.2020.117542DOI Listing
May 2020

Near-infrared/pH dual-responsive nanocomplexes for targeted imaging and chemo/gene/photothermal tri-therapies of non-small cell lung cancer.

Acta Biomater 2020 04 7;107:242-259. Epub 2020 Mar 7.

Cancer Metastasis Alert and Prevention Center, College of Chemistry, Fuzhou University, 2 Xueyuan Road, Yangguang Building, 6FL, Fuzhou 350108, China; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou 350108, China. Electronic address:

Combination therapy offers promising opportunities for treating advanced non-small cell lung cancer (NSCLC). Here, we established a chitosan-based nanocomplex CE7Q/CQ/S to deliver molecular-targeted drug erlotinib (Er), Survivin shRNA-expressing plasmid (SV), and photothermal agent heptamethine cyanine dye (Cy7) in one platform for simultaneous near-infrared (NIR) fluorescence imaging and triple-combination therapy of NSCLC bearing epidermal growth factor receptor (EGFR) mutations. The obtained CE7Q/CQ/S exhibited favorable photothermal effects, good DNA binding ability, and pH/NIR dual-responsive release behaviors. The conjugated Er could mediate specific delivery of Cy7 to EGFR-mutated NSCLC cells to enable targeted NIR fluorescence imaging and photothermal therapy (PTT). The in vitro and in vivo results showed that downregulation of Survivin expression and the photothermal effects could act synergistically with Er to induce satisfactory anticancer effects in either Er-sensitive or Er-resistant EGFR-mutated NSCLC cells. By integrating chemo/gene/photothermal therapies into one theranostic nanoplatform, CE7Q/CQ/S could significantly suppress EGFR-mutated NSCLC, indicating its potential use in treating NSCLC. STATEMENT OF SIGNIFICANCE: The development of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has improved overall survival in patients with NSCLC driven by EGFR mutations. Unfortunately, the emergence of acquired resistance of EGFR-TKIs is almost inevitable after treatment. Here, we constructed a NIR/pH dual-responsive nanocomplex CE7Q/CQ/S based on chitosan which could integrate targeted near-infrared fluorescence imaging and chemo/gene/phototheramal tri-therapies together. We found that CE7Q/CQ/S possessed a promising outcome in fighting against EGFR-mutated NSCLC. The inhibition of Survivin expression and the application of photothermal therapy could act synergistically with erlotinib and reverse erlotinib resistance. The results of this work suggested that this chitosan-based combination therapeutic nanoplatform could be a promising candidate for NSCLC treatment.
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http://dx.doi.org/10.1016/j.actbio.2020.03.004DOI Listing
April 2020

Modeling counter-current chromatography with non-ideal injection.

J Chromatogr A 2020 Jun 18;1620:460983. Epub 2020 Feb 18.

School of Mechanical Engineering, Sichuan University, Chengdu 610065, China.

In general counter-current chromatography systems, there are several off-column fittings between injector and column inlet, such as bends, valves, connecting tubes and joints. Due to these off-column fittings, the sample will diffuse in the mobile phase and form an irregular distribution when it flows from the injector to the column inlet. Thus, the concentration distribution of the solutes at the column inlet is a continuous curve (called the injection profile). As some previous research reveals, it is necessary to input actual injection profile into the simulation model to mimic elution profile. Therefore, we built a non-ideal CCC model whose initial value is from the actual injection profile, and validated the rationality of this model with iteration method. The simulation analysis of different injection profiles shows the conditions whereby a discrete injection profile can replace the actual injection profile in the non-ideal CCC model for accurate simulation elution. Simulation elution under such conditions reveal that non-ideal injection model can reflect the relationship between the injection profile and elution profile, and help to explain the reasons of irregular change in elution profile, like the tailed peak and flat peak.
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http://dx.doi.org/10.1016/j.chroma.2020.460983DOI Listing
June 2020

Mifepristone Derivative FZU-00,003 Suppresses Triple-negative Breast Cancer Cell Growth partially via miR-153-KLF5 axis.

Int J Biol Sci 2020 1;16(4):611-619. Epub 2020 Jan 1.

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Chinese Academy of Sciences, Kunming Institute of Zoology, Kunming, Yunnan 650223, China.

Triple-negative breast cancer (TNBC) is one of the most malignant breast cancers lacking targeted therapeutics currently. We recently reported that mifepristone (MIF), a drug regularly used for abortion, suppresses TNBC cell growth by inhibiting KLF5 expression via inducing miR-153. However, its anticancer efficacy is only modest at high dose. In order to enhance the anticancer activities, a focused compound library containing 17 compounds by altering the sensitive metabolic region of mifepristone has been designed and synthesized. We first tested the cell growth inhibitory effects of these compounds in TNBC cell lines. Among them, FZU-00,003 displayed the most potent efficiency. FZU-00,003 suppresses TNBC cell growth, cell cycle progression and induces apoptosis more effectively than MIF does. Consistently, FZU-00,003 induces miR-153 expression and suppressed KLF5 expression at much lower dosages than MIF does. Furthermore, FZU-00,003 inhibits tumor growth more potently than MIF does. Taken together, the MIF derivative, FZU-00,003 may serve as a better therapeutic compound for TNBC than MIF.
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http://dx.doi.org/10.7150/ijbs.39491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990921PMC
February 2021

E35 ablates acute leukemia stem and progenitor cells in vitro and in vivo.

J Cell Physiol 2020 11 21;235(11):8023-8034. Epub 2020 Jan 21.

Department of Hematology, Fujian Institute of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.

Leukemia stem cells (LSCs) have critical functions in acute leukemia (AL) pathogenesis, participating in its initiation and relapse. Thus, identifying new molecules to eradicate LSCs represents a high priority for AL management. This work identified E35, a novel Emodin derivative, which strongly inhibited growth and enhanced apoptosis of AL stem cell lines, and primary stem and progenitor cells from AL cases, while sparing normal hematopoietic cells. Furthermore, functional assays in cultured cells and animals suggested that E35 preferentially ablated primitive leukemia cell populations without impairing their normal counterparts. Moreover, molecular studies showed that E35 remarkably downregulated drug-resistant gene and dramatically inhibited the Akt/mammalian target of rapamycin signaling pathway. Notably, the in vivo anti-LSC activity of E35 was further confirmed in murine xenotransplantation models. Collectively, these findings indicate E35 constitutes a novel therapeutic candidate for AL, potentially targeting leukemia stem and progenitor cells.
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http://dx.doi.org/10.1002/jcp.29457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540425PMC
November 2020

Nanoparticle-based drug delivery systems for controllable photodynamic cancer therapy.

Eur J Pharm Sci 2020 Mar 10;144:105213. Epub 2020 Jan 10.

Cancer Metastasis Alert and Prevention Center, College of Chemistry, Fuzhou University, 2 Xueyuan Road, Yangguang Building, 6FL., Fuzhou, Fujian 350108, China; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, 2 Xueyuan Road, Yangguang Building, 6FL., Fuzhou, Fujian 350108, China. Electronic address:

Compared with the traditional treatment, photodynamic therapy (PDT) in the treatment of malignant tumors has the advantages of less damage to normal tissues, quick therapeutic effect, and ability to repeat treatments to the same site. However, most of the traditional photosensitizers (PSs) have severe skin photosensitization, poor tumor targeting, and low therapeutic effect in hypoxic tumor environment, which limit the application of PDT. Nanoparticle-based drug delivery systems can improve the targeting of PSs and release drugs with controllable photoactivity at predetermined locations, so as to achieve desired therapeutic effects with minimal side-effects. The present review summarizes the current nanoparticle platforms for PDT, and offers the description of different strategies including tumor-targeted delivery, controlled-release of PSs and the triggered photoactivity to achieve controllable PDT by nanoparticle-based drug delivery systems. The challenges and prospects for further development of intelligent PSs for PDT are also discussed.
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http://dx.doi.org/10.1016/j.ejps.2020.105213DOI Listing
March 2020

Progress and Challenges Toward the Rational Design of Oxygen Electrocatalysts Based on a Descriptor Approach.

Adv Sci (Weinh) 2020 Jan 27;7(1):1901614. Epub 2019 Nov 27.

Department of Electronics National Institute for Advanced Materials Renewable Energy Conversion and Storage Center Tianjin Key Laboratory of Photo-Electronic Thin Film Device and Technology Nankai University Tianjin 300071 China.

Oxygen redox catalysis, including the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), is crucial in determining the electrochemical performance of energy conversion and storage devices such as fuel cells, metal-air batteries,and electrolyzers. The rational design of electrochemical catalysts replaces the traditional trial-and-error methods and thus promotes the R&D process. Identifying descriptors that link structure and activity as well as selectivity of catalysts is the key for rational design. In the past few decades, two types of descriptors including bulk- and surface-based have been developed to probe the structure-property relationships. Correlating the current descriptors to one another will promote the understanding of the underlying physics and chemistry, triggering further development of more universal descriptors for the future design of electrocatalysts. Herein, the current benchmark activity descriptors for oxygen electrocatalysis as well as their applications are reviewed. Particular attention is paid to circumventing the scaling relationship of oxygen-containing intermediates. For hybrid materials, multiple descriptors will show stronger predictive power by considering more factors such as interface reconstruction, confinement effect, multisite adsorption, etc. Machine learning and high-throughput simulations can thus be crucial in assisting the discovery of new multiple descriptors and reaction mechanisms.
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http://dx.doi.org/10.1002/advs.201901614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947511PMC
January 2020

MUC-1 recognition-based activated drug nanoplatform improves doxorubicin chemotherapy in breast cancer.

Cancer Lett 2020 03 16;472:165-174. Epub 2019 Dec 16.

Department of Breast Surgery, Henan Provincial People's Hospital, Zhengzhou, 450003, China; Department of Breast Surgery, Zhengzhou University People's Hospital, Zhengzhou, 450003, China; Department of Breast Surgery, Henan University People's Hospital, Zhengzhou, 450003, China. Electronic address:

Tumor-targeted drug delivery systems with stimuli-response drug release have been increasingly used to improve the therapeutic efficacy of antitumor drugs. Here, we report a specific molecular recognition activation drug nanoplatform based on specially designed DNA sensor-capped doxorubicin (DOX)-loaded mesoporous silica nanoparticles (MSNs), designated as specific molecular recognition-activated nanoparticle (SMRAN). DNA sensors on the targeted nanoparticles can trigger DOX release through a conformational switch induced by MUC-1. This causes a significant difference in cell viability between breast cancer MCF-7 and normal breast Hs578bst cells (24.8% and 86.0%). In vivo experiments showed that the tumor volume was reduced 1.5-times in the SMRAN treatment group. Compared with that in the DOX group, due to significantly improved tumor accumulation and retention of DOX. The strategy of the MUC-1 activated drug delivery system is expected to provide a new perspective for clinical application.
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http://dx.doi.org/10.1016/j.canlet.2019.12.019DOI Listing
March 2020

Construction of Bisindolines via Oxidative Coupling Cyclization.

Org Lett 2020 Jan 12;22(1):116-119. Epub 2019 Dec 12.

Key Laboratory of Molecule Synthesis and Function Discovery (Fujian Province University), College of Chemistry , Fuzhou University , Fuzhou , Fujian 350116 , China.

Herein, we report a general approach for the efficient construction of three-dimensional bisindolines via oxidative coupling cyclization in an intermolecular manner. This reaction is featured by its operational simplicity, metal-free conditions, lack of protecting group, and high selectivity. Notably, a wide range of anilines are suitable in this intermolecular cyclization, furnishing corresponding bisindolines in up to 98% yield.
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http://dx.doi.org/10.1021/acs.orglett.9b04037DOI Listing
January 2020

Synthesis and potent cytotoxic activity of a novel diosgenin derivative and its phytosomes against lung cancer cells.

Beilstein J Nanotechnol 2019 24;10:1933-1942. Epub 2019 Sep 24.

Cancer Metastasis Alert and Prevention Center, College of Chemistry, Fuzhou University, Fuzhou, Fujian 350116, China.

Diosgenin (Di), a steroidal sapogenin derived from plants, has been shown to exert anticancer effects in preclinical studies. Using Di as a starting material, various Di derivatives were designed and synthesized, aiming to discover new steroid-based antitumor agents. In this work, we synthesized several Di derivatives and screened FZU-0021-194-P2 (P2), which showed more potent cytotoxic activities against human non-small-cell lung cancer A549 and PC9 cells. Considering that Di has a unique sterol structure similarly to cholesterol, P2 phytosomes (P2Ps) were prepared to further improve the water solubility of P2. The P2Ps exhibited a particle size of 53.6 ± 0.3 nm with oval shape and a zeta potential of -4.0 ± 0.7 mV. P2Ps could inhibit the proliferation of lung cancer cells more efficiently than Di phytosomes after 72 h of incubation time by inducing cell cycle arrest and apoptosis. The results indicated that P2Ps could be a promising anticancer formulation for non-small-cell lung cancer.
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http://dx.doi.org/10.3762/bjnano.10.189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774070PMC
September 2019