Publications by authors named "Zhipeng Chen"

169 Publications

Advances in chlorin-based photodynamic therapy with nanoparticle delivery system for cancer treatment.

Expert Opin Drug Deliv 2021 Jul 15:1-27. Epub 2021 Jul 15.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, PR, China.

: The treatment of tumors is one of the most difficult problems in the medical field at present. Patients often use a comprehensive therapy that combines surgery, radiotherapy, and chemotherapy. Photodynamic therapy (PDT) has prominent potential for eradicating various cancers. Chlorin-based photosensitizers (PSs), as one of the most utilized photosensitizers, have many advantages over conventional photosensitizers; however, a successful chlorin-based PDT needs multi-functional nano-carriers for selective photosensitizer delivery. The number of researches about nanoparticles designed for improved chlorin-based PSs is increasing in the current era. In this article, we give a brief review focused on the recent research progress in design of chlorin-based nanoparticles for the treatment of malignant tumors with photodynamic therapy.: This review focuses on the current nanoparticle platforms for PDT, and describes different strategies to achieve controllable PDT by chlorin-nano-delivery systems. The challenges and prospects of PDT in clinical applications are also discussed.: The requirement for PDT to eradicate cancers has increased exponentially in recent years. The major clinically used photosensitizers are hydrophobic. The main obstacles in effective delivery of PSs are associated with this intrinsic nature. The design of nano-delivery systems to load PSs is pivotal for PSs' widespread use.
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http://dx.doi.org/10.1080/17425247.2021.1950685DOI Listing
July 2021

Design of fast response Doppler spectroscopy system for HUST field-reversed configuration device.

Rev Sci Instrum 2021 Jun;92(6):063522

International Joint Research Laboratory of Magnetic Confinement Fusion and Plasma Physics, State Key Laboratory of Advanced Electromagnetic Engineering and Technology, School of Electrical and Electronic Engineering, Huazhong University of Science and Technology, Wuhan 430074, China.

A fast response Doppler spectroscopy system with high throughput and high resolution is under development for studying the drifting velocity, rotation velocity, and ion temperature on the HUST field-reversed configuration (HFRC) device. The system has been designed to observe the spectral line of oxygen V (O V) ion emission at 278.1 nm (1s2s3p → 1s2s3s) over the lifetime (∼0.5 ms) of the FRC plasma. A high throughput Czerny-Turner monochromator with 3600 g/mm grating and 670 mm focal length is applied to achieve high spectral resolution; a 32-channel multi-anode photomultiplier tube (PMT) detector is utilized to achieve the high-speed response of up to 1 MHz; a 1D magnification optics combined with a cylindrical lens assembly and a fiber optic expansion is developed to magnify the spectral dispersion fitting the PMT channel interval. Through the ray-tracing analysis, the system's final spectral resolution is evaluated to be ∼0.03 nm. Taking into account the system sensitivity and O V line emissivity in HFRC plasma, the system is expected to be workable with the temporal response of 1 µs.
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http://dx.doi.org/10.1063/5.0043310DOI Listing
June 2021

Comparison of Percutaneous Kyphoplasty and Pedicle Screw Fixation for Treatment of Thoracolumbar Severe Osteoporotic Vertebral Compression Fracture with Kyphosis.

World Neurosurg 2021 Jun 12. Epub 2021 Jun 12.

Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China; Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China. Electronic address:

Background: Pedicle screw fixation (PSF) has been considered the preferred surgery for the treatment of severe osteoporotic vertebral compression fracture (sOVCF), and sOVCF was traditionally regarded as a relative contraindication to minimally invasive percutaneous kyphoplasty (PKP). Debate has continued regarding the selection of the best surgical method for sOVCF. In the present study, we compared the efficacy and safety between PKP and PSF.

Methods: PKP was performed in 376 patients in group 1 and PSF in 121 patients in group 2. The visual analog scale (VAS), Oswestry disability index (ODI), local kyphotic angle, fractured vertebral body height, and complications were evaluated.

Results: In the immediate postoperative analysis, the mean VAS score for group 1 was 2.4, significantly lower than the VAS score of 4.7 for group 2. The mean ODI score was 44.4% for group 1, lower than the ODI score of 57.1% for group 2. In addition, group 1 had had a significantly better ODI score at 1 year of follow-up. The local kyphotic angle and fractured vertebral body height had recovered better in group 2. In group 1, 113 patients had experienced cement leakage, and 29 patients had undergone PKP for adjacent new vertebral fractures. In group 2, 2 patients had developed wound infections, 4 had developed pneumonia, 2 had developed urinary tract infection, 3 had experienced asymptomatic screw loosening, and 7 had undergone PKP to treat new vertebral fractures and 1 had undergone removal of internal fixation because of back pain.

Conclusions: The results of the clinical and radiological evaluations showed that PKP is comparable to PSF for the treatment of sOVCF with kyphosis, with PKP having the advantages of minimal invasion, quick postoperative pain relief, and functional recovery.
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http://dx.doi.org/10.1016/j.wneu.2021.06.030DOI Listing
June 2021

The Efficacy of Intra-Arterial Plus Intravesical Chemotherapy Intravesical Chemotherapy Alone After Bladder-Sparing Surgery in High-Risk Bladder Cancer: A Systematic Review and Meta-Analysis of Comparative Study.

Front Oncol 2021 27;11:651657. Epub 2021 May 27.

Department of Urology, Beijing TianTan Hospital, Capital Medical University, Beijing, China.

Background: Due to the poor prognosis, the treatment of high-risk bladder cancer (HRBC) remains controversial. This meta-analysis aims to access the efficacy of intra-arterial chemotherapy (IAC) combined with intravesical chemotherapy (IC) IC alone after bladder-sparing surgery in HRBC.

Methods: A systematic search of PubMed, Cochrane Library databases, EMBASE (until June 2020) was conducted. PRISMA checklist was followed. The data were analyzed by RevMan v5.3.0.

Results: A total of five articles including 843 patients were studied. The analysis demonstrated that the IAC + IC group had a greater improvement of overall survival (P = 0.02) and significant reduction in terms of tumor recurrence rate (P = 0.0006) and tumor progression rate (P = 0.008) compared with the IC group. The recurrence-free survival in the IAC + IC group was significantly higher than that in the IC group (P = 0.004), but there was no significant difference in progression-free survival between the two groups (P = 0.32). In addition, the combination of IAC and IC significantly extended tumor recurrence interval (P = 0.0001) and reduced tumor-specific death rate (P = 0.01) for patients with HRBC compared with IC alone. For side effects related with IAC, although about half of the patients experienced some toxicities, most of them were mild and reversible (grades 1-2, 22.3% . grade 3-4, 2.7%), mainly including nausea/vomiting (P = 0.0001), neutropenia (P = 0.002), and alanine aminotransferase (P = 0.0001).

Conclusion: Patients with HRBC treated with IAC + IC after bladder-sparing surgery had a marked improvement in the overall survival, recurrence-free survival, time interval to first recurrence, tumor recurrence rate, tumor progression rate, and tumor-specific death rate than patients treated with IC alone. However, progression-free survival was not significantly correlated with treatment strategy. In addition, patients seemed to tolerate well the toxicities related with IAC.

Systematic Review Registration: PROSPERO, identifier CRD42021232679.
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http://dx.doi.org/10.3389/fonc.2021.651657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190377PMC
May 2021

High prevalence of osteoporosis in patients undergoing spine surgery in China.

BMC Geriatr 2021 06 13;21(1):361. Epub 2021 Jun 13.

Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Background: With the increase in life expectancy, a large number of patients with osteoporosis (OP) are undergoing spine surgery, which may adversely affect the surgical success rate. The prevalence of OP varies in different regions, and no data are available that represent the prevalence of OP among Chinese patients over 50 years of age who are undergoing spine surgery. It was the first multicenter study to assess OP in these patients. Aiming to obtain comprehensive data, this study combined bone mineral density (BMD) measurements and visual radiography assessment (VRA) to analyze the prevalence of OP in patients aged > 50 years who underwent spine surgery.

Methods: Data from 1,856 patients aged over 50 years undergoing spine surgery who resided in northern, central, and southern China were reviewed between 2018 and 2019. Based on the perioperative BMD and X-ray data, we calculated the prevalence of OP in this special population according to sex, age, and spine degenerative disease.

Results: A total of 1,245 patients (678 females and 567 males) were included in the study. The prevalence of OP diagnosed by BMD was 52.8 % in females and 18.7 % in males. When we combined with BMD and VRA, the prevalence of OP increased from 52.8 to 65.9 % in females and from 18.7 to 40.6 % in males. Although OP was more severe in females than in males, a significant difference in the rate of vertebral fracture (VF) was not observed between females and males with a normal BMD and osteopenia (females vs. males: aged 50-59 years, P = 0.977; 60-69 years, P = 0.302; >70 years, P = 0.172). Similarly, no significant difference in the vertebral fracture rate was observed within different age groups of patients with a normal BMD and osteopenia (females: P = 0.210; males, P = 0.895). The incidence of OP in patients with degenerative scoliosis was higher than that in the remaining patients (females: 63.6 % vs. 42.4 %, P = 0.018; males: 38.9 % vs. 13.8 %, P = 0.004).

Conclusions: A high prevalence of OP was identified in patients aged > 50 years undergoing spine surgery, especially in patients whose primary diagnosis was degenerative scoliosis. BMD and VRA evaluations should be included in the clinical routine for these patients prior to surgery.
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http://dx.doi.org/10.1186/s12877-021-02313-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201731PMC
June 2021

Sensitivity and Stability of Functional Vision Tests in Detecting Subtle Changes Under Multiple Simulated Conditions.

Transl Vis Sci Technol 2021 06;10(7)

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Purpose: To explore whether subtle changes in visual quality can be detected using different measures of visual function against the quick contrast sensitivity function test (quick CSF).

Methods: Sixty participants, aged 17 to 34 years, were enrolled. Participants' vision was degraded by 0.25 D undercorrection (0.25 D), 60% neutral density filter brightness reduction (60% ND), and 0.8 Bangerter foil optical diffusion (0.8BAN). Visual function tests including visual acuity and contrast sensitivity (CSV-1000E and quick CSF) were measured with participant's best-corrected vision and under simulated visual degradation conditions. Test sensitivities in detecting differences were compared.

Results: Statistically significant visual acuity degradation was observed in the 0.8BAN condition only (Pcorrected < 0.001). With CSV-1000E and outliers removed, significant CS degradation was observed in all spatial frequencies, area under log CSF (AULCSF) in the 0.8BAN condition (Pcorrected < 0.001 for all), medium and high spatial frequencies and AULCSF in the 60%ND condition (Pcorrected,6cpd = 0.002, Pcorrected,12cpd = 0.005, Pcorrected,18cpd = 0.001, Pcorrected,AULCSF < 0.001) and the 0.25 D condition (Pcorrected,6cpd = 0.011, Pcorrected,12cpd = 0.013, Pcorrected,18cpd = 0.015, Pcorrected,AULCSF < 0.001). With the quick CSF, significant CS degradation was observed in all simulated visual conditions in all spatial frequencies, cutoff frequency and AULCSF (Pcorrected < 0.001 for all). Test-retest reliability of the quick CSF method was high; coefficient of repeatability ranged from 0.14 to 0.18 logCS.

Conclusions: Compared with visual acuity and chart-based CS tests, the quick CSF method provided more reliable and sensitive measures to detect small visual changes.

Translational Relevance: The quick CSF method can provide sensitive and reliable measures to monitor disease progression and assess treatment outcomes.
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http://dx.doi.org/10.1167/tvst.10.7.7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196408PMC
June 2021

Use of zero-profile device for contiguous three-level anterior cervical discectomy and fusion: comparison with cage and plate construct.

J Neurosurg Spine 2021 Jun 4:1-8. Epub 2021 Jun 4.

1Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou; and.

Objective: The aim of this study was to compare a traditional cervical cage with a zero-profile (ZP) fixation device in patients who underwent three-level anterior cervical decompression and fusion (ACDF) in terms of patient-reported outcomes (visual analog scale [VAS], Japanese Orthopaedic Association [JOA], and Neck Disability Index [NDI] scores), radiographic findings (sagittal alignment 2 years after surgery and likelihood of fusion), and complications.

Methods: This study was a retrospective case series. Between January 2012 and December 2016, 58 patients with cervical spondylotic myelopathy (CSM) who required three-level ACDF procedures, as identified by spinal surgeons, were treated with three-level ACDF and an anterior cage-plate construct (ACPC) (n = 38) or a three-level stand-alone ZP device (n = 20). On the basis of patient choice, patients were divided into two groups (ACPC group and ZP group). All patients completed a minimum of 2 years of follow-up. Patient-reported outcome scores included VAS, JOA, and NDI scores. The radiographic findings included sagittal alignment and likelihood of fusion 2 years after surgery. Data related to patient-reported outcomes and sagittal alignment were collected preoperatively, postoperatively, and at the final follow-up. Intraoperative and postoperative complications were also documented and analyzed.

Results: The clinical outcomes, including VAS, JOA, and NDI scores, showed improvement in both groups, and no significant difference was observed between the two groups. Sagittal alignment and height of the fused segments were restored in all patients. However, the authors found no differences between the ZP and ACPC groups, and the groups exhibited similar fusion rates. The authors found no differences in complications, including dysphagia, adjacent-segment degeneration, and postoperative hematoma, between the groups.

Conclusions: Use of ZP implants yielded satisfactory long-term clinical and radiological outcomes that were similar to those of the standard ACPC. Additionally, the rates of complications between the groups were not significantly different. Although the best surgical option for multilevel CSM remains controversial, the results of this work suggest that ACDF with the ZP device is feasible, safe, and effective, even for multilevel CSM.
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http://dx.doi.org/10.3171/2020.11.SPINE201319DOI Listing
June 2021

Multifunctional nanorods based on self-assembly of biomimetic apolipoprotein E peptide for the treatment of Alzheimer's disease.

J Control Release 2021 Jul 1;335:637-649. Epub 2021 Jun 1.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address:

Targeting a single molecule or a single pathway and poor drug delivery to the brain hamper the therapy of Alzheimer's disease (AD) based on abnormal metabolism of amyloid-β (Aβ). To solve these problems, we designed and synthesized a multi - strategy peptide (MOP), an ingenious apolipoprotein E mimetic peptide, which could reduce Aβ deposition via inhibiting Aβ aggregation and at the same time accelerate Aβ clearance. Meanwhile, MOP could be self-assembled into different nanostructure, thus we constructed a multifunctional delivery system (APND-3) based on MOP self-assembled nanorods (aspect ratios of 3) that was a favorable morphology to enhance the permeation across the blood brain barrier (BBB) to address the poor delivery to brain issues. Besides, the drug delivery system introduces polydopamine (PDA) and COG1410 ligand as a shell to keep the favorable morphology of core and enhance the BBB targeting efficiency. As a result, the delivery system significantly enhances the delivery of MOP to the brain, thus reducing Aβ deposition, mitigating the memory deficits, and ameliorating neurologic damage in AD model mice. Our findings suggest that our drug and carrier integrated multifunctional delivery system has the potential for AD treatment.
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http://dx.doi.org/10.1016/j.jconrel.2021.05.044DOI Listing
July 2021

Design, Synthesis, and Structure-Activity Relationship of -Aryl-'-(thiophen-2-yl)thiourea Derivatives as Novel and Specific Human TLR1/2 Agonists for Potential Cancer Immunotherapy.

J Med Chem 2021 06 24;64(11):7371-7389. Epub 2021 May 24.

Guangdong Provincial Key Laboratory of New Drug Screening and Guangzhou Key Laboratory of Drug Research for Emerging Virus Prevention and Treatment, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.

The previous virtual screening of ten million compounds yielded two novel nonlipopeptide-like chemotypes as TLR2 agonists. Herein, we present the chemical optimization of our initial hit, 1-phenyl-3-(thiophen-2-yl)urea, which resulted in the identification of SMU-C80 (EC = 31.02 ± 1.01 nM) as a TLR2-specific agonist with a 370-fold improvement in bioactivity. Mechanistic studies revealed that SMU-C80, through TLR1/2, recruits the adaptor protein MyD88 and triggers the NF-κB pathway to release cytokines such as TNF-α and IL-1β from human, but not murine, cells. To the best of our knowledge, it is the first species-specific TLR1/2 agonist reported until now. Moreover, SMU-C80 increased the percentage of T, B, and NK cells and activated the immune cells, which suppressed cancer cell growth . In summary, we obtained a highly efficient and specific human TLR1/2 agonist that acts through the MyD88 and NF-κB pathway, facilitating cytokine release and the simultaneous activation of immune cells that in turn affects the apoptosis of cancer cells.
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http://dx.doi.org/10.1021/acs.jmedchem.0c02266DOI Listing
June 2021

Targeting hyperactive TGFBR2 for treating MYOCD deficient lung cancer.

Theranostics 2021 3;11(13):6592-6606. Epub 2021 May 3.

MOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.

Clinical success of cancer therapy is severely limited by drug resistance, attributed in large part to the loss of function of tumor suppressor genes (TSGs). Developing effective strategies to treat those tumors is challenging, but urgently needed in clinic. MYOCD is a clinically relevant TSG in lung cancer patients. Our and data confirm its tumor suppressive function. Further analysis reveals that MYOCD potently inhibits stemness of lung cancer stem cells. Mechanistically, MYOCD localizes to TGFBR2 promoter region and thereby recruits PRMT5/MEP50 complex to epigenetically silence its transcription. NSCLC cells deficient of MYOCD are particularly sensitive to TGFBR kinase inhibitor (TGFBRi). TGFBRi and stemness inhibitor synergize with existing drugs to treat MYOCD deficient lung cancers. Our current work shows that loss of function of MYOCD creates Achilles' heels in lung cancer cells, which might be exploited in clinic.
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http://dx.doi.org/10.7150/thno.59816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120205PMC
July 2021

An injectable peptide hydrogel with excellent self-healing ability to continuously release salvianolic acid B for myocardial infarction.

Biomaterials 2021 07 29;274:120855. Epub 2021 Apr 29.

College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China. Electronic address:

Drug-loaded hydrogels can improve blood supply and inhibit extracellular matrix degradation after myocardial infarction. However, due to the continual dynamic motion of cardiac tissue, the hydrogel structure cannot be reconstructed in time, causing accelerated degradation and drug burst release. Here, a novel, superior, self-healing elastin-mimic peptide hydrogel (EMH) was fabricated for the local delivery of salvianolic acid B (SaB). The self-healing ability of EMH is enhanced by SaB-loaded polydopamine nanoparticles (SaB-PDA). In vitro, the pre-hydrogel (SaB-PDA/pre-EMH) is endowed with excellent biocompatibility and a low viscosity, making it suitable for intramyocardial injection. Once injected into the myocardial infarction (MI) region, SaB-PDA/pre-EMH can form SaB-PDA/EMH with great mechanical strength under the action of upregulated transglutaminase (TGase) in heart tissue post-MI. The superior self-healing ability of SaB-PDA/EMH allows for an increase in retention time in the beating ventricular wall. Therefore, with long-term release of SaB, SaB-PDA/EMH can inhibit ventricular remodeling and promote angiogenesis for MI treatment.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120855DOI Listing
July 2021

Automated Generation of Personalized Shock Wave Lithotripsy Protocols: Treatment Planning Using Deep Learning.

JMIR Med Inform 2021 May 11;9(5):e24721. Epub 2021 May 11.

School of Medicine, University of Utah, Salt Lake City, UT, United States.

Background: Though shock wave lithotripsy (SWL) has developed to be one of the most common treatment approaches for nephrolithiasis in recent decades, its treatment planning is often a trial-and-error process based on physicians' subjective judgement. Physicians' inexperience with this modality can lead to low-quality treatment and unnecessary risks to patients.

Objective: To improve the quality and consistency of shock wave lithotripsy treatment, we aimed to develop a deep learning model for generating the next treatment step by previous steps and preoperative patient characteristics and to produce personalized SWL treatment plans in a step-by-step protocol based on the deep learning model.

Methods: We developed a deep learning model to generate the optimal power level, shock rate, and number of shocks in the next step, given previous treatment steps encoded by long short-term memory neural networks and preoperative patient characteristics. We constructed a next-step data set (N=8583) from top practices of renal SWL treatments recorded in the International Stone Registry. Then, we trained the deep learning model and baseline models (linear regression, logistic regression, random forest, and support vector machine) with 90% of the samples and validated them with the remaining samples.

Results: The deep learning models for generating the next treatment steps outperformed the baseline models (accuracy = 98.8%, F1 = 98.0% for power levels; accuracy = 98.1%, F1 = 96.0% for shock rates; root mean squared error = 207, mean absolute error = 121 for numbers of shocks). The hypothesis testing showed no significant difference between steps generated by our model and the top practices (P=.480 for power levels; P=.782 for shock rates; P=.727 for numbers of shocks).

Conclusions: The high performance of our deep learning approach shows its treatment planning capability on par with top physicians. To the best of our knowledge, our framework is the first effort to implement automated planning of SWL treatment via deep learning. It is a promising technique in assisting treatment planning and physician training at low cost.
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http://dx.doi.org/10.2196/24721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150413PMC
May 2021

Tumor-associated macrophages secret exosomal miR-155 and miR-196a-5p to promote metastasis of non-small-cell lung cancer.

Transl Lung Cancer Res 2021 Mar;10(3):1338-1354

Department of Thoracic Surgery, Jiangsu Province People's Hospital and the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: Understanding the molecular basis underlying metastasis of non-small cell lung cancer (NSCLC) may provide a new therapeutic modality for the treatment of NSCLC. However, the mechanisms by which tumor-associated macrophages (TAMs) affect NSCLC metastasis remain undefined. In this study, we aimed to discover a novel regulatory pathway involved in NSCLC metastasis.

Methods: Cell Counting Kit-8 (CCK-8), Transwell, western blot assays were used to assess cell viability, migration, invasion and epithelial-mesenchymal transition (EMT). Exosomes from macrophages medium were characterized, and in vitro cell coculture was further conducted to investigate M2 derived exosomes mediated crosstalk between TAMs and tumor cells. Besides, miRNA microarray was used to analyze miRNA expression profiles of M0 and M2 derived exosomes. Luciferase reporter assay was used to verify the potential binding between miRNA and mRNA. Moreover, 6-week-old male BALB/c nude mice were performed to establish transplantation tumor model using tail vein injection. Hematoxylin & eosin staining was used to detect the metastasis of tumor tissues.

Results: We found that M2 TAMs were the main TAMs in metastatic tissues of NSCLC patients and exosomes derived from M2 TAMs were able to promote cell viability, cell migration, cell invasion and EMT in NSCLC. We demonstrated that miR-155 and miR-196a-5p were abundant in M2 TAMs and exosomes secreted by M2 TAMs. Functional experiments demonstrated that the deletion of miR-155 and miR-196a-5p in M2 TAMs significantly prevented NSCLC metastasis and . To clarify the mechanism governing miR-155 and miR-196a-5p from M2 TAMs, we carried out bioinformatics analysis to predict potential target genes. Mechanistically, miR-155 and miR-196a-5p directly bound to the 3'-UTR of Ras association domain family member 4 (RASSF4), and negatively regulating RASSF4 expression. At last, rescue assays demonstrated that miR-155 and miR-196a-5p exerted its performance by RASSF4.

Conclusions: Overall, we revealed a new regulatory pathway that was M2 TAMs secreted exosomal miR-155 and miR-196a-5p to promote NSCLC metastasis. This dynamic and reciprocal cross-talk between NSCLC and macrophages innovatively provided a potential opportunity for diagnosis and treatment of NSCLC.
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http://dx.doi.org/10.21037/tlcr-20-1255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044469PMC
March 2021

Enhanced Embolization Efficacy with the Embolic Microspheres Guided by the Aggregate Gradation Theory Through In Vitro and Simulation Evaluation.

Cardiovasc Eng Technol 2021 Apr 12. Epub 2021 Apr 12.

School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, 510006, Guangdong, People's Republic of China.

Purpose: Size of the embolic microspheres is of critical importance in the transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) to achieve the optimal embolization therapy. In this regard, to optimize the size distribution of the embolic microspheres and enhance the embolization efficacy, the aggregate gradation theory is used to formulate the microspheres.

Methods: Finite element analysis (FEA) and in vitro experiments confirmed a better embolic efficacy for the poly(vinyl alcohol) (PVA) microspheres formulated according to the aggregate gradation theory.

Results: The average volume flow of the graded group was 1.31 × 10 mL/s in vitro experiment, which was lowest among all the groups suggesting the graded group had the optimal embolic effect. The graded group has the largest pressure gradient of 314.22 Pa/μm in FEA among all the groups, which can be attributed to the highest packing density of the graded group compared with other groups.

Conclusions: The graded embolic microspheres have a larger drag coefficient compared with the narrow size distribution groups both in vitro experiment and FEA. These findings can be used to formulate the embolic agents with optimal size distributions and are significant for the improvement of clinical embolization therapy.
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http://dx.doi.org/10.1007/s13239-021-00534-xDOI Listing
April 2021

Zeolitic imidazolate framework-8/ fluorinated graphene coated SiO composites for pipette tip solid-phase extraction of chlorophenols in environmental and food samples.

Talanta 2021 Jun 18;228:122229. Epub 2021 Feb 18.

School of Chemical Engineering and Pharmacy, Key Laboratory for Green Chemical Process of Ministry of Education, Wuhan Institute of Technology, Wuhan, 430205, China. Electronic address:

In this work, a novel composite adsorbent was successfully prepared by zeolite imidazolate framework-8/fluorinated graphene layer-by-layer covalently bonded on SiO microspheres, and followed to be packed into micro pipette tip for extraction of trace chlorophenols prior to their detection by high performance liquid chromatography (HPLC). The morphology and structure of adsorbent material was characterized by field emission scanning electron microscopy with energy dispersive spectrometer, X-ray diffraction, and N adsorption. The parameters including the amount of adsorbent, sampling volume, sampling rate, sample pH, and desorption solvent affected the extraction performance was systematically investigated by pipette tip solid-phase extraction (PT-SPE) coupled with HPLC analysis. Under the optimized condition, the linearity of this method ranged from 20 to 2000 ng mL for chlorophenols (CPs) with determination coefficient higher than 0.99. The limit of detection (at a signal-to-noise ratio of 3) were in the range 2-20 ng mL for tap water and black tea drinks, 0.2-2 μg g for honey. The relative recoveries of the CPs from spiked samples ranged from 71.8% to 104.7%, with relative standard deviations less than 6.2%. The filled extraction tube exhibited good stability and reproducibility. The proposed method has been successfully used to detect CPs in water and drinks with satisfactory recoveries.
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http://dx.doi.org/10.1016/j.talanta.2021.122229DOI Listing
June 2021

An evolved native microalgal consortium-snow system for the bioremediation of biogas and centrate wastewater: Start-up, optimization and stabilization.

Water Res 2021 May 10;196:117038. Epub 2021 Mar 10.

Jiangsu Key Laboratory of Chemical Pollution Control and Resources Reuse, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Xiao Ling Wei 200, Nanjing 210094, Jiangsu, China. Electronic address:

It is necessary to develop sustainable technologies for centrate wastewater (CW) and biogas treatment from sludge anaerobic digestion (AD) systems in an environmentally friendly and economical manner. The microalgae-based bioremediation approach presents a competitive alternative due to its capacity for nutrient recovery and carbon sequestration. However, process instabilities and operating challenges limit its development and implementation largely due to the complexities in the CW and biogas. In this study, the evolved native microalgal consortium (ENMC) was firstly developed using the gradual stress increase method to enhance their adaptation in high ammonium condition. The supplementation of local snow (with Ca and Mg) and biogas into CW significantly enhanced ENMC growth through batch tests. Subsequently, an integrated ENMC-snow (ENMCS) system was proposed consisting of a hydrolysis-acidification reactor (HAR), biogas upgrade reactor, and photobioreactor (PBR). The ENMCS system was systematically investigated under both batch and semi-continuous operations, by adjusting primary process parameters including the fill ratio, feeding time, hydraulic retention time (HRT), wastewater pretreatment, and PBR type. It was eventually optimized as a 24 h, 70% fermented CW diluted with 30% snow water, semi-continuous feeding system with a fill ratio of 50% and HRT of 6 d in an open-PBR. Long-term operation (310 days) showed superior biomass yield (0.3059 ± 0.0039 g/(L•d)) and nutrient removal efficiencies (95.6 ± 0.13% and 90.8 ± 0.44% for NH-N and PO-P removal). Meanwhile, biogas was upgraded with an 82.2% CO reduction. The economic and environmental analysis further demonstrated the ENMCS system as an effective alternative for the bioremediation of AD effluents while simultaneously producing value-added biomass, especially applicable to snowy regions.
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http://dx.doi.org/10.1016/j.watres.2021.117038DOI Listing
May 2021

Effect of Teriparatide on pain relief, and quality of life in postmenopausal females with osteoporotic vertebral compression fractures, a retrospective cohort study.

Ann Palliat Med 2021 Apr 1;10(4):4000-4007. Epub 2021 Mar 1.

Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Background: Osteoporotic vertebral compression fracture (OVCF) is a common disease in elderly population, which could cause serious back pain and has a substantial impact on patients' health-related quality of life (HRQoL). The aim of this study was to identify the effect of Teriparatide as a conservative treatment on reducing back pain, and improving quality of life for postmenopausal women with osteoporotic vertebral fractures.

Methods: In a 12-month, retrospective study, 112 postmenopausal women with OVCFs were assigned to Teriparatide group (20 µg Teriparatide, subcutaneous, once daily, n=38) or control group (500 mg calcium and 400-800 IU Vitamin D per day, oral administration, n=74) according to patients' choices between January 2016 and October 2018. Patient-reported outcomes scores including the visual analogue score (VAS), Oswestry disability index (ODI), and short form 36 questionnaire (SF-36) were assessed at baseline, the 3rd months, the 6th months and 1 year after treatment.

Results: Treatments with Teriparatide or calcium plus vitamin D supplements had significant effect on improvement of patients' back pain as well as HRQoL, with significantly reduced VAS and ODI and increased SF-36 physical component summary (PCS) and mental component summary (MCS) scores. At the endpoint, Teriparatide showed better therapeutic effect, with greater reductions in VAS and ODI and more increases in SF-36 PCS and MCS scores. However, more adverse events (AEs) were found in Teriparatide group, but symptoms were relatively mild and of short duration.

Conclusions: In postmenopausal women with OVCFs, the consequent persistent back pain and impaired HRQoL, treatment with Teriparatide was associated with more profound therapeutic effects and more AEs compared with calcium plus vitamin D supplements.
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http://dx.doi.org/10.21037/apm-20-2333DOI Listing
April 2021

Preparation and evaluation of oral self-microemulsifying drug delivery system of Chlorophyll.

Drug Dev Ind Pharm 2021 Jul 21:1-10. Epub 2021 Jul 21.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, PR China.

Objective: This study was aimed at improving the water solubility and oral bioavailability of Chl by self-microemulsifying drug delivery system (Chl-SMEDDS).

Methods: Compatibility experiments, pseudo-ternary phase diagram and central composite design were used to optimize the formulation. The selected systems were further evaluated for physical characteristics, including particle size, zeta potential, and appearance. The stability, dispersion test, and intestinal perfusion experiments were used to evaluate the SMEDDS.

Results: The optimal composition of Chl-SMEDDS included: Labrafil M 1944 CS (35%), kolliphor RH 40 (46%), Transcutol HP (19%) and 60 mg/g Chl. The appearance of water emulsified Chl-SMEDDS was green and transparent. The particle size, ζ-potential, and transmission electron microscopy studies showed that spherical globules of Chl-SMEDDS with a size of about 22.82 ± 1.29 nm and a negative surface charge of -24.21 ± 3.45 mV were obtained. Chl-SMEDDS could remain stable at 25 °C and 4 °C for at least 6 months. The dispersion test showed that Chl-SMEDDS dispersed spontaneously to form microemulsion after disintegration of capsule shell and 90% drug dispersed in just 30 min in pH 1.2 HCl without any drug precipitation during the test period. intestinal perfusion experiment revealed that the main absorption site for Chl-SMEDDS was duodenum.

Conclusions: This study indicates that SMEDDS formulation could be an effective strategy for the oral administration of Chl.
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http://dx.doi.org/10.1080/03639045.2021.1892746DOI Listing
July 2021

Design of a dispersion interferometer on a field-reversed configuration device.

Rev Sci Instrum 2021 Feb;92(2):023508

International Joint Research Laboratory of Magnetic Confinement Fusion and Plasma Physics, State Key Laboratory of Advanced Electromagnetic Engineering and Technology, School of Electrical and Electronic Engineering, Huazhong University of Science and Technology, Wuhan 430074, China.

Dispersion interferometry (DI) is a promising method for density measurement. Compared with the traditional interferometer, the DI is immune to mechanical vibration and can avoid the fringe jump error. In addition, a simple optical configuration is also one of the advantages of the DI. The electron density of the Huazhong University of Science and Technology field-reversed configuration (HFRC) device can reach 10 m with a pulse length of 50 µs. In this case, the DI based on the CO laser on the HFRC device adopts the heterodyne technique based on the acousto-optic modulator, which can increase the temporal resolution to 40 MHz. It can realize density fluctuation measurements in the MHz range. The test of each optical element, especially the nonlinear crystal, has been completed. The AgGaSe crystal can produce a second harmonic wave of about 52.5 µW when the incident CO power is 10 W. Based on these designs and tests, a DI system can be expected on the HFRC device.
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http://dx.doi.org/10.1063/5.0040484DOI Listing
February 2021

Systematic review and meta-analysis of the efficacy and safety of vibegron vs antimuscarinic monotherapy for overactive bladder.

Medicine (Baltimore) 2021 Feb;100(5):e23171

Department of Urology.

Background: Vibegron is a new β3-adrenergic receptor agonist which has been demonstrated for the treatment of overactive bladder (OAB). We carried out meta-analysis to evaluate the efficiency of vibegron vs antimuscarinic monotherapy for treating OAB.

Methods: Randomized controlled trials (RCTs) of Vibegron vs antimuscarinic monotherapy for OAB were searched systematically by using EMBASE, MEDLINE, and the Cochrane Controlled Trials Register. The RevMan version 5.3.0. was used to analysis the data.

Results: Three RCTs involving a total of 1751 patients were studied in the Systematic review and Meta-analysis. Efficacy end points: the mean number of micturitions episodes/d (P = .16); the mean number of urgency episodes/d (P = .05); mean number of urgency incontinence episodes/d (P = .11) and mean number of incontinence episodes/d (P = .14) indicated that vibegron and antimuscarinic had no significant differences in terms of OAB treatment. Mean volume voided/micturition showed a distinct difference in the two groups (P = .009). With regard to dry mouth and drug related treatment-emergent adverse event (TEAE), vibegron showed better tolerance than antimuscarinic. Serious adverse event (SAE) and discontinuations due to adverse event (AE) did not show a significant difference between the two groups.

Conclusions: The therapeutic effect of vibegron is similar to that of antimuscarinic, but vibegron does not increase the risk of AE.
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http://dx.doi.org/10.1097/MD.0000000000023171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870164PMC
February 2021

Short-term response to immune-chemotherapy and immune features of a ceritinib-resistant patient with -rearranged lung adenocarcinoma.

J Immunother Cancer 2021 Feb;9(2)

Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China

Patients with -rearranged non-small cell lung cancer (NSCLC) inevitably relapse after first-line targeted therapy with tyrosine kinase inhibitors. Efficacy of checkpoint inhibitor-based therapy on -positive NSCLC in second-line setting and change of immune factors during treatment are rarely studied. We report a -rearranged stage ⅢB lung adenocarcinoma patient who was resistant to ceritinib after developing a secondary F2004L mutation. He received eight cycles of nivolumab plus chemotherapy and had an initial partial response, but brain metastases appeared in the seventh cycle. Lorlatinib was confirmed to have activity against with F2004L in vitro, and was administered to this patient as the third-line therapy. The patient responded well to lorlatinib and had no relapse. We explored the tumor immune microenvironment (TIME) during immune-chemotherapy by multiplex immunohistochemistry, RNA sequencing, and multiplex plasma protein immunoassay. The results show that the TIME was active and plasma inflammatory factors were increased when the patient responded to immune-chemotherapy, while the plasma inhibitory checkpoint proteins, lymphocyte-activation gene 3, B and T lymphocyte attenuator, programmed cell death ligand 1 (PD-L1), and PD-1, were increased when the disease progressed. Moreover, the PD-L1 expression on tumor tissue was upregulated during treatment, predicting the limited benefit from immune-chemotherapy. This case report suggests that lorlatinib is a better choice than immune-chemotherapy in second-line setting for patients with similar genomic characteristics, and that monitoring the immune components during immunotherapy may help to predict disease response.
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http://dx.doi.org/10.1136/jitc-2020-001967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871696PMC
February 2021

An Upstream Open Reading Frame in Phosphatase and Tensin Homolog Encodes a Circuit Breaker of Lactate Metabolism.

Cell Metab 2021 01;33(1):128-144.e9

Department of Neurosurgery, Institute of Precision Medicine, the First Affiliated Hospital of Sun Yat-sen University, Guangdong Provincial Key Laboratory of Brain Function and Disease, Sun Yat-sen University, Guangzhou, Guangdong 510080, China. Electronic address:

The metabolic role of micropeptides generated from untranslated regions remains unclear. Here we describe MP31, a micropeptide encoded by the upstream open reading frame (uORF) of phosphatase and tensin homolog (PTEN) acting as a "circuit breaker" that limits lactate-pyruvate conversion in mitochondria by competing with mitochondrial lactate dehydrogenase (mLDH) for nicotinamide adenine dinucleotide (NAD). Knocking out the MP31 homolog in mice enhanced global lactate metabolism, manifesting as accelerated oxidative phosphorylation (OXPHOS) and increased lactate consumption and production. Conditional knockout (cKO) of MP31 homolog in mouse astrocytes initiated gliomagenesis and shortened the overall survival of the animals, establishing a tumor-suppressing role for MP31. Recombinant MP31 administered intraperitoneally penetrated the blood-brain barrier and inhibited mice GBM xenografts without neurological toxicity, suggesting the clinical implication and application of this micropeptide. Our findings reveal a novel mode of MP31-orchestrated lactate metabolism reprogramming in glioblastoma.
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http://dx.doi.org/10.1016/j.cmet.2020.12.008DOI Listing
January 2021

4D Printing of Magnetoactive Soft Materials for On-Demand Magnetic Actuation Transformation.

ACS Appl Mater Interfaces 2021 Jan 5;13(3):4174-4184. Epub 2021 Jan 5.

Guangdong Provincial Key Laboratory of Sensor Technology and Biomedical Instrument, School of Biomedical Engineering, Sun Yat-Sen University, Guangzhou 510085, P. R. China.

Four-dimensional (4D) printed magnetoactive soft material (MASM) with a three-dimensional (3D) patterned magnetization profile possesses programmable shape transformation and controllable locomotion ability, showing promising applications in actuators and soft robotics. However, typical 4D printing strategies for MASM always introduced a printing magnetic field to orient the magneto-sensitive particles in polymers. Such strategies not only increase the cooperative control complexity of a 3D printer but may also induce local agglomeration of magneto-sensitive particles, which disturbs the magnetization of the already-printed structure. Herein, we proposed a novel 4D printing strategy that coupled the traditional 3D injection printing with the origami-based magnetization technique for easy fabrication of MASM objects with a 3D patterned magnetization profile. The 3D injection printing that can rapidly create complex 3D structures and the origami-based magnetization technique that can generate the spatial magnetization profile are combined for fabrication of 3D MASM objects to yield programmable transformation and controllable locomotion. A physics-based finite element model was also developed for the design guidance of origami-based magnetization and magnetic actuation transformation of MASM. We further demonstrated the diverse functions derived from the complex shape deformation of MASM-based robots, including a bionic human hand that played "rock-paper-scissors" game, a bionic butterfly that swung the wings on the flower, and a bionic turtle that crawled on the land and swam in the water.
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http://dx.doi.org/10.1021/acsami.0c19280DOI Listing
January 2021

Photoselective sharp enucleation of the prostate with a front-firing 532-nm laser: an innovative surgical technique for benign prostatic hyperplasia-a single-center study of 475 cases.

World J Urol 2021 Jan 3. Epub 2021 Jan 3.

Urological Institution of the People's Liberation Army, First Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, China.

Purpose: To describe the novel technique of photoselective sharp enucleation of the prostate (PSEP) with a front-firing 532-nm laser and evaluate its efficacy and safety.

Methods: A seven-step standardized surgical procedure was established, and PSEP was performed in an en bloc or lobulate manner according to the size of the middle lobe of the prostate. The following clinical data of 583 patients who underwent PSEP in our center from November 2016 to May 2018 were retrospectively reviewed: maximum flow rate (Q), International Prostate Symptom Score (IPSS), quality of life score (Q), post-void residual volume (PVR), prostate volume, operation time, serum prostate-specific antigen (PSA) concentration, and complications at 1, 6, and 12 months postoperatively.

Results: Of the 583 patients, 475 had complete clinical information and were included in the study. The median operation time was 39 min. There were significant improvements in the Q, IPSS, Q, PVR and PSA concentration at each follow-up time point postoperatively. Postoperative hemorrhage occurred in 22 patients (4.6%), urinary retention in 29 (6.1%), urinary tract infection in 55 (11.6%), bladder neck contracture in 8 (1.7%), urethral strictures in 11 (2.3%), and stress urinary incontinence in 9 (1.9%).

Conclusions: PSEP is effective and safe for the treatment of benign prostatic hyperplasia. The innovative technique integrates the excellent hemostatic property of the 532-nm laser and the high efficiency of enucleation. It decreases the occurrence of postoperative incontinence associated with "blunt" enucleation of 532-nm laser and eliminates the lack of tissue samples problem associated with photoselective vaporization of the prostate.
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http://dx.doi.org/10.1007/s00345-020-03547-8DOI Listing
January 2021

Programmable Transformation and Controllable Locomotion of Magnetoactive Soft Materials with 3D-Patterned Magnetization.

ACS Appl Mater Interfaces 2020 Dec 15;12(52):58179-58190. Epub 2020 Dec 15.

Guangdong Provincial Key Laboratory of Sensor Technology and Biomedical Instrument, School of Biomedical Engineering, Sun Yat-sen University, Guangzhou 510275 PR China.

Magnetoactive soft material (MASM) is distinguished for multifunctional shape manipulations under magnetic actuation, thereby holding a great promise in soft robotics, actuators, electronics, and metamaterials. However, the current research of MASM with continuum hard-magnetic profiles focuses little on the transformation mechanism, high dimensional shape transformation, and multistable locomotion. Herein, we developed a systematic methodology for programmable transformation and controllable locomotion of MASM with 3D-patterned continuum magnetization. An iterative computational model based on the equilibrium between magnetic torque and deformation-induced elastic torque was developed for precise prediction of MASM transformation. Multidimensional and complex shape manipulation ability of MASM was demonstrated by magnetically actuated transformations, including 1D to 2D, 2D to 3D, and 3D to 4D transformations of solid MASM, 2D to 3D pattern transformation of MASM-based elastin-like mesh, and 3D to 4D transformation of MASM-based cuboidal lattice. Multistable and controllable locomotion of MASM was verified by multimodal locomotion behaviors of a scallop-inspired robot for wall climbing in a dry frame and drug delivery in wet stomach, including roll, open, and close under self-locked and unlocked states.
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http://dx.doi.org/10.1021/acsami.0c15406DOI Listing
December 2020

Iron accumulation in macrophages promotes the formation of foam cells and development of atherosclerosis.

Cell Biosci 2020 Nov 26;10(1):137. Epub 2020 Nov 26.

Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, 210093, People's Republic of China.

Background: Macrophages that accumulate in atherosclerotic plaques contribute to progression of the lesions to more advanced and complex plaques. Although iron deposition was found in human atherosclerotic plaques, clinical and pre-clinical studies showed controversial results. Several epidemiological studies did not show the positive correlation between a systemic iron status and an incidence of cardiovascular diseases, suggesting that the iron involvement occurs locally, rather than systemically.

Results: To determine the direct in vivo effect of iron accumulation in macrophages on the progression of atherosclerosis, we generated Apoe mice with a macrophage-specific ferroportin (Fpn1) deficiency (ApoeFpn1). Fpn1 deficiency in macrophages dramatically accelerated the progression of atherosclerosis in mice. Pathophysiological evidence showed elevated levels of reactive oxygen species, aggravated systemic inflammation, and altered plaque-lipid composition. Moreover, Fpn1 deficiency in macrophages significantly inhibited the expression of ABC transporters (ABCA1 and ABCG1) by decreasing the expression of the transcription factor LXRα, which reduced cholesterol efflux and therefore promoted foam cell formation and enhanced plaque formation. Iron chelation relieved the symptoms moderately in vivo, but drastically ex vivo.

Conclusions: Macrophage iron content in plaques is a critical factor in progression of atherosclerosis. The interaction of iron and lipid metabolism takes place in macrophage-rich atherosclerotic plaques. And we also suggest that altering intracellular iron levels in macrophages by systemic iron chelation or dietary iron restriction may be a potential supplementary strategy to limit or even regress the progression of atherosclerosis.
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http://dx.doi.org/10.1186/s13578-020-00500-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691057PMC
November 2020

Lactoferrin/phenylboronic acid-functionalized hyaluronic acid nanogels loading doxorubicin hydrochloride for targeting glioma.

Carbohydr Polym 2021 Feb 10;253:117194. Epub 2020 Oct 10.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, PR China. Electronic address:

Herein, lactoferrin (Lf)/phenylboronic acid (PBA)-functionalized hyaluronic acid nanogels crosslinked with disulfide-bond crosslinker was developed as a reduction-sensitive dual-targeting glioma therapeutic platform for doxorubicin hydrochloride (DOX) delivery (Lf-DOX/PBNG). Spherical Lf-DOX/PBNG with optimized physicochemical properties was obtained, and it could rapidly release the encapsulated DOX under high glutathione concentration. Moreover, enhanced cytotoxicity, superior cellular uptake efficiency, and significantly improved brain permeability of Lf-DOX/PBNG were observed in cytological studies compared with those of DOX solution, DOX-loaded PBA functionalized nanogels (DOX/PBNG), and Lf modified DOX-loaded nanogels (Lf-DOX/NG). The pharmacokinetic study exhibited that the area under the curve of DOX/PBNG, Lf-DOX/NG, and Lf-DOX/PBNG increased by 8.12, 4.20 and 4.32 times compared with that of DOX solution, respectively. The brain accumulation of Lf-DOX/PBNG was verified in biodistribution study to be 12.37 and 4.67 times of DOX solution and DOX/PBNG, respectively. These findings suggest that Lf-DOX/PBNG is an excellent candidate for achieving effective glioma targeting.
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http://dx.doi.org/10.1016/j.carbpol.2020.117194DOI Listing
February 2021

Inactivation of tumor suppressor gene Clusterin leads to hyperactivation of TAK1-NF-κB signaling axis in lung cancer cells and denotes a therapeutic opportunity.

Theranostics 2020 16;10(25):11520-11534. Epub 2020 Sep 16.

Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes and MOE Key Laboratory of Tumor Molecular Biology, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.

Clinical success of precision medicine is severely limited by de novo or acquired drug resistance. It remains a clinically unmet need to treat these patients. Tumor suppressor genes (TSGs) play a critical role in tumorigenesis and impact the therapeutic effect of various treatments. Using clinical data, cell line data and mouse model data, we revealed the tumor suppressive role of Clusterin in lung cancer. We also delineated the signaling cascade elicited by loss of function of CLU in NSCLC cells and tested precision medicine for deficient lung cancers. is a potent and clinically relevant TSG in lung cancer. Mechanistically, CLU inhibits TGFBR1 to recruit TRAF6/TAB2/TAK1 complex and thus inhibits activation of TAK1- NF-κB signaling axis. Lung cancer cells with loss of function of CLU show exquisite sensitivity to TAK1 inhibitors. Importantly, we show that a significant portion of Kras mutation positive NSCLC patients are concurrently deficient of CLU and that TAK1 kinase inhibitor synergizes with existing drugs to treat this portion of lung cancers patients. Combinational treatment with TAK1 inhibitor and MEK1/2 inhibitor effectively shrank Kras mutation positive and CLU deficient NSCLC tumors. Moreover, we put forward a concept that loss of function of a TSG rewires signaling network and thereby creates an Achilles' heel in tumor cells which could be exploited in precision medicine.
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http://dx.doi.org/10.7150/thno.44829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545994PMC
June 2021

Establishment of a UPLC-MS/MS Method for Studying the Effect of Salt-Processing on Tissue Distribution of Twelve Major Bioactive Components of Qing'e Pills in Rats.

J Anal Methods Chem 2020 17;2020:8832736. Epub 2020 Sep 17.

College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.

Qing'e pills is clinically used for treating osteoporosis in postmenopausal women in China. Eucommiae Cortex and Psoraleae Fructus are the main herbs of Qing'e pills and are both required to be salt-processed. In order to study the influence of salt-processing on the tissue distribution of Qing'e pills, a UPLC-MS/MS method was established for studying the tissue distribution of 12 main bioactive ingredients of Qing'e pills in rats. The linear relationships of the 12 compounds in each tissue were good. The method was fully validated for its selectivity, accuracy, precision, stability, matrix effect, and extraction recovery. Then, the validated method was successfully applied for simultaneous determination of the 12 chemical components in Qing'e pills in tissues for the first time. Areas under the curve (AUC) results showed that, except for pinoresinol diglucoside, psoralen, and isopsoralen, the distribution of the other components was increased in the kidney, uterus, ovary, and testes. Relative targeting efficiency (RTE) results showed that all 12 chemical components targeted the kidney and sexual organs. The results indicated that the Eucommiae Cortex and Psoraleae Fructus after salt-processing could significantly increase the distribution of components to the kidney and generative organs.
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http://dx.doi.org/10.1155/2020/8832736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519442PMC
September 2020
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