Publications by authors named "Hongtao Zhang"

325 Publications

A mouse model of ankle-subtalar joint complex instability induced post-traumatic osteoarthritis.

J Orthop Surg Res 2021 Sep 1;16(1):541. Epub 2021 Sep 1.

Department of Orthopedics, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, 215006, Jiangsu, People's Republic of China.

Background: Ankle-subtalar joint complex instability is not uncommonly presented in the clinic, but symptoms and signs similar to other conditions can easily lead to its misdiagnosis. Due to the lack of appropriate animal models, research on ankle-subtalar joint complex instability is limited. The aims of the present study were to establish an animal model of ankle-subtalar joint complex instability in mice and to explore its relationship with post-traumatic osteoarthritis (PTOA).

Methods: Twenty-one male C57BL/6J mice were randomly divided into three groups: SHAM group (sham surgery group), transected cervical ligament + anterior talofibular ligament (CL+ATFL) group, and transected cervical ligament + deltoid ligament (CL+DL) group. Two weeks after surgery, all mice underwent cage running training. Balance beam and gait tests were used to evaluate the changes in self-movement in the mice after ankle-subtalar ligament injury. Micro-CT and histological staining were used to evaluate the progress of PTOA.

Results: Compared with the SHAM group, balance and gait were affected in the ligament transection group. Twelve weeks after surgery, the time required to cross the balance beam in the CL+ATFL group was 35.1% longer and the mice slipped 3.6-fold more often than before surgery, and the mean step length on the right side was 7.2% smaller than that in the SHAM group. The time required to cross the balance beam in the CL+DL group was 32.1% longer and the mice slipped 3-fold more often than prior to surgery, and the average step length on the right side was 5.6% smaller than that in the SHAM group. CT images indicated that 28.6% of the mice in the CL+DL group displayed dislocation of the talus. Tissue staining suggested that articular cartilage degeneration occurred in mice with ligament transection 12 weeks after surgery.

Conclusions: Transected mice in the CL+ATFL and CL+DL groups displayed mechanical instability of the ankle-subtalar joint complex, and some mice in the CL+DL group also suffered from talus dislocation due to ligament injury leading to loss of stability of the bone structure. In addition, as time progressed, the articular cartilage displayed degenerative changes, which affected the ability of animals to move normally.
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http://dx.doi.org/10.1186/s13018-021-02683-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408979PMC
September 2021

Rational design of 17β-hydroxysteroid dehydrogenase type3 for improving testosterone production with an engineered Pichia pastoris.

Bioresour Technol 2021 Aug 25;341:125833. Epub 2021 Aug 25.

Chemical Engineering Research Center, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, PR China; State Key Laboratory of Chemical Engineering, Tianjin University, Tianjin 300350, PR China.

Testosterone (TS) is a critical androgenic steroid that regulates human metabolism and maintains secondary sexual characteristics. The biotransformation from 4-androstene-3,17-done (4-AD) to TS is limited by the poor catalytic activity of 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3). Herein, we explored the structural characteristics and catalytic mechanism of 17β-HSD3 and adopted the rational design strategy to improve its catalytic activity. Molecular docking and molecular dynamics simulations revealed the substrate-binding pocket and the binding mode of 4-AD to 17β-HSD3. We located the pivotal residues and regulated their hydrophobicity and polarity. The obtained G186R/Y195W variant formed additional electrostatic interaction and hydrogen bond with 4-AD, increasing the binding affinity between the variant and 4-AD. Therefore, the G186R/Y195W variant produced 3.98 g/L of TS, which increased to 297%. The combination of structural and mechanism resolution drives the implementation of the rational design strategy, which provides guidance for bioproduction of TS catalyzed by 17β-HSD3.
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http://dx.doi.org/10.1016/j.biortech.2021.125833DOI Listing
August 2021

Rational Design of Constrained Peptides as Protein Interface Inhibitors.

Antibodies (Basel) 2021 Aug 16;10(3). Epub 2021 Aug 16.

Department of Pathology and Laboratory of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

The lack of progress in developing targeted therapeutics directed at protein-protein complexes has been due to the absence of well-defined ligand-binding pockets and the extensive intermolecular contacts at the protein-protein interface. Our laboratory has developed approaches to dissect protein-protein complexes focusing on the superfamilies of erbB and tumor necrosis factor (TNF) receptors by the combined use of structural biology and computational biology to facilitate small molecule development. We present a perspective on the development and application of peptide inhibitors as well as immunoadhesins to cell surface receptors performed in our laboratory.
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http://dx.doi.org/10.3390/antib10030032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395526PMC
August 2021

Bifunctional utilization of whey powder as a substrate and inducer for β-farnesene production in an engineered Escherichia coli.

Bioresour Technol 2021 Aug 9;341:125739. Epub 2021 Aug 9.

Chemical Engineering Research Center, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, PR China; State Key Laboratory of Chemical Engineering, Tianjin University, Tianjin 300072, PR China.

β-Farnesene can replace petroleum products as specialty fuel to solve the global fuel energy crisis, but its production by Escherichia coli (E.coli) using glucose and isopropyl β-D-1-thiogalactopyranoside (IPTG) is costly. Hence, we developed a new strategy to produce β-farnesene by engineered E.coli strain F13 with bifunctional utilization of whey powder. The utilization of whey powder as a substrate ensured the growth of the strain F13, while whey powder could also replace IPTG to induce the production of β-farnesene. In shake flasks, β-farnesene production reached 2.41 g/L by the bifunctional utilization of whey powder as a substrate and inducer, 65.1% higher than that with IPTG and glucose. In the 7 L bioreactor, β-farnesene production reached 4.74 g/L using whey powder, which was 197% of that in shake flasks. Therefore, this new strategy might be an attractive route to broaden the applications of whey powder and achieve the economical production of β-farnesene.
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http://dx.doi.org/10.1016/j.biortech.2021.125739DOI Listing
August 2021

Visual Mechanism Characteristics of Static Painting Based on PSO-BP Neural Network.

Comput Intell Neurosci 2021 9;2021:3835083. Epub 2021 Aug 9.

Shool of Foreign Studies, Henan Polytechnic University, Jiaozuo, Henan 454003, China.

Static painting works have independent theme significance in the framework of Chinese painting history, and their overall structure, lightness structure, and color structure all show different characteristics of visual mechanism. In order to extract the visual mechanism features effectively, this experiment uses the PSO algorithm to optimize the BP neural network, constructs the PSO-BP neural network for feature recognition and extraction, and compares it with the training results of other algorithms. The results show that the prediction accuracy, recognition accuracy, and ROC curve of PSO-BP neural network are high, which shows that the convergence of PSO-BP neural network is good, and it can effectively complete the recognition and analysis of people and effectively extract the visual mechanism features of static writing paintings.
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http://dx.doi.org/10.1155/2021/3835083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370825PMC
August 2021

Advances in clinical immunotherapy for gastric cancer.

Biochim Biophys Acta Rev Cancer 2021 Aug 14;1876(2):188615. Epub 2021 Aug 14.

Research Center, the Fourth Hospital of Hebei Medical University, Shijiazhuang, China. Electronic address:

Gastric cancer (GC) is one of the most malignant human cancers with increasing incidence worldwide, ranking among the top five malignant tumors worldwide in terms of incidence and mortality. The clinical efficacy of conventional therapies is limited, and the median overall survival (mOS) for advanced-stage gastric cancer is only about 8 months. Emerging as one of breakthroughs for cancer therapy, immunotherapy has become an effective treatment modality after surgery, chemotherapy, radiotherapy, and targeted therapy. In this review, we have summarized the progresses of clinical development of immunotherapies for gastric cancer. Major advances with immune checkpoint inhibitors (ICIs) have started to change the clinical practice for gastric cancer treatment and prognosis. Additionally, combination therapies with other modalities, such as targeted therapies, are expected to push immunotherapies to front-line. In this review, the efficacy of ICIs and targeted therapy alone or combination with existing therapies gastric cancer treatment was described and the predictive value of biomarkers for immunotherapies in gastric cancer treatment is also discussed.
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http://dx.doi.org/10.1016/j.bbcan.2021.188615DOI Listing
August 2021

Comparison of three-dimensional-printed template-guided and traditional implantation of I seeds for gynecological tumors: A dosimetric and efficacy study.

J Cancer Res Ther 2021 Jul;17(3):688-694

Department of Oncology, Hebei Medical University, No.361 East Zhongshan Road; Department of Oncology, Hebei General Hospital, Shijiazhuang, Hebei, China.

Objective: The objective of the study was to compare the dose parameter and clinical efficacy of three-dimensional-printed template (3D-PT)-guided and traditional I seed implantation in treatment of gynecological tumors.

Materials And Methods: A total of 28 patients with gynecological tumors treated with radioactive seed implantation in Hebei General Hospital from January 2016 to December 2018 were retrospectively analyzed. Twelve patients (template group) were guided by 3D-PT and the remaining 16 patients (traditional group) were guided by computed tomography (CT) with traditional technique. Preoperative treatment plan (preplan) was completed through a treatment planning system. In the template group, 3D-PT was printed according to preplan and seeds were implanted under the guidance of 3D-PT and CT. In the traditional group, seeds were implanted under the guidance of single CT directly according to the preplan. Postoperative verification plan (post-plan) was completed. Dose-volume histogram (DVH) was calculated and D80, D90, V90, V100, and V150 were obtained according to DVH. Then, deviation of the dosimetric parameters D80, D90, V90, V100, and V150 between the preplan and postplan were compared within the two groups. The difference and percentage of difference of the above dosimetric parameters between the preplan and postplan within the two groups were calculated using the formula X = X X, and X% = (X X)/X × 100%. Doses were calculated to determine whether the differences there were statistically significant. Efficacy evaluation was completed according to RECISIT 1.1. Local control rate and effective rate of 2-months postplan were compared between the two groups. Survival analysis was completed by the Kaplan-Meier method. The patients were followed up for 12 months, and their survival rate was calculated and compared.

Results: There was no significant difference between the two groups for all the parameters, except for D80 of the preplan and postplan in the traditional group (P = 0.000). All the differences and percentage of difference were calculated and it was found that the X difference of D80 (P = 0.035), D90 (P = 0.023), V90 (P = 0.047), V100 (P = 0.032), and V150 (P = 0.031), as well as the X% difference of D80 (P = 0.032), D90 (P = 0.034), V90 (P = 0.042), V100 (P = 0.036), and V150 (P = 0.044) of the two groups was statistically significant, thus indicating that the dosimetric parameter fluctuation in the template group was more stable. The result of the curative effect after 2 months were as follows: the local control rate and effective rate of the template group were 100% (12/12) and 83.3% (10/12), while those of the traditional group were 100% (16/16) and 81.2% (13/16). There was no statistically significant difference in the curative effect between the two groups. After 6-27 months (median = 12 months) of follow-up, the median survival time of the template group and traditional group were 17 (10-23) and 16 (11-20) months, respectively, and the 1-year overall survival rate was 63% and 79% (P = 0.111), respectively, with no statistically significant difference observed.

Conclusion: 3D-PT-guided I seed implantation is safe and effective in the treatment of gynecological tumors.
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http://dx.doi.org/10.4103/jcrt.JCRT_1565_20DOI Listing
July 2021

Effect of Zoledronic Acid on the Vertebral Body Bone Mineral Density After Instrumented Intervertebral Fusion in Postmenopausal Women With Osteoporosis.

Global Spine J 2021 Jul 2:21925682211027833. Epub 2021 Jul 2.

Department of Orthopedics, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.

Study Design: Retrospective cohort study.

Objectives: To evaluate the effect of zoledronic acid, an anti-osteoporosis treatment, during the perioperative period on vertebral body bone mineral density (BMD) after spinal fusion surgery in postmenopausal women with osteoporosis.

Methods: The medical records of postmenopausal patients with osteoporosis who underwent instrumented intervertebral fusion for lumbar degenerative disease between July 2016 and May 2018 were reviewed. Patients with comorbidities or condition which might affect bone metabolism were excluded. Forty-six patients did not receive anti-osteoporosis treatment before surgery and during the postoperative follow-up (untreated group). Another 46 patients who was treated with zoledronic acid perioperatively were matched for age and body mass index to patients in the untreated group. Preoperative and postoperative dual-energy X-ray absorptiometry (DEXA) records and lumbar BMD values of the involved spinal segments and of the cephalad levels, as well as of the femoral neck were recorded.

Results: A significant decrease of cephalad vertebral BMD values was observed in the untreated group (-11.47%, < ), with a slight decrease of the femoral neck (-1.28%, > ). Zoledronic acid prevented rapid bone loss after instrumented intervertebral fusion surgery, with a bone loss in the cephalad levels of -0.76 ± 4.71% compared to -11.47 ± 16.45% in the untreated group ( < ). while the change in BMD of the femoral neck in the treated group was 1.52 ± 5.88% compared to -1.28 ± 6.58% in the untreated group ( = ).

Conclusions: Perioperative zoledronic acid treatment may offer protection against a significant decrease in BMD of cephalad vertebrae after spinal fusion surgery among postmenopausal women with osteoporosis.
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http://dx.doi.org/10.1177/21925682211027833DOI Listing
July 2021

Dosimetry study of three-dimensional print template for 125I implantation therapy.

Radiat Oncol 2021 Jun 24;16(1):115. Epub 2021 Jun 24.

Department of Oncology, Hebei General Hospital, 348 West Heping Road, Shijiazhuang, 050051, Hebei, China.

Background: I seed implantation has been found to show good therapeutic effects on tumors. Recent studies showed that three-dimensional (3D) print template-assisted I seed implantation can optimize radiation dose distribution. This study aimed to compare the dose distribution differences in I seed implantation among 3D print noncoplanar template- (3DPNCT), 3D print coplanar template- (3DPCT) assisted implantation and traditional free-hand implantation.

Methods: We systematically searched the PubMed, EMbase, Cochrane Library, Wan Fang Med Online, China National Knowledge Infrastructure (CNKI) from the earliest to November 2020 without time or language restrictions. And the references of primary literature were also searched. The outcome measures were dosimetry and operation time. This meta-analysis was carried out using Stata 12.0.

Results: A total of 16 original articles were selected for inclusion. The differences of D90, D100, V90, and V100 values pre- and post-implantation with traditional free-hand implantation showed statistically significant (p < 0.05). The differences of D90, D100, V100, V150, V200, and D2cc of organs at risk (OAR) values pre- and post-implantation with 3D print template showed no statistically significant (p > 0.05). Compared with traditional free-hand implantation without any templates, 3D print template could improve postoperative D90 (Standard mean difference, SMD = 0.67, 95% confidence interval (CI) = 0.35 to 0.98, p < 0.001), D100 (SMD = 0.82, 95%CI = 0.40 to 1.23, p < 0.001), V90 (SMD = 1.48, 95%CI = 0.95 to 2.00, p < 0.001), V100 (SMD = 1.41, 95%CI = 0.96 to 1.86, p < 0.001), and reduce operation time (SMD = - 0.93, 95%CI = - 1.34 to - 0.51, p < 0.001). In three studies, both 3DPNCT and 3DPCT plans were designed for all patients. The prescribed dose and seed activity were same. Pooled analysis of D90, D100, V100, D2cc of OAR, number of seeds and number of needles showed no significant differences between 3DPNCT and 3DPCT groups (p > 0.05). However, in 3DPNCT group, V150 and V200 were increased (SMD = 0.35, 0.49; 95%CI = 0.04 to 0.67, 0.02 to 0.96; p = 0.028, 0.043); the number of through bone needles was reduced (SMD = - 1.03, 95%CI = - 1.43 to - 0.64, p < 0.001).

Conclusions: Compared with traditional free-hand implantation, 3D print template-assisted I seeds implantation can optimize dose distribution and reduce the implantation time at the same time. Compared with 3D print coplanar template, 3D print noncoplanar template can increase the volume of high dose within tumor target and is more safer in the respect of puncture route.
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http://dx.doi.org/10.1186/s13014-021-01845-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223396PMC
June 2021

Synthesis of functional oligosaccharides and their derivatives through cocultivation and cellular NTP regeneration.

Adv Appl Microbiol 2021 3;115:35-63. Epub 2021 May 3.

Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, Jiangsu, China.

Carbohydrates play an important role in the life cycle. Among them, functional oligosaccharides show a complex and diverse structures with unique physiological activities and biological functions. However, different preparation methods directly affect the structure, molecular weight, and other functions of oligosaccharides, as well as their application fields and manufacturing costs. In the preparation of β-1,3-glucan oligosaccharides (OBGs), water insolubility of β-1,3-glucans hampers the hydrolysis efficiency. The synthesis of some functional oligosaccharides requires the consumption of energy substrates, such as ATP, CTP, and uridine triphosphate, for sugar nucleotide synthesis, leading to increased capital costs. A more economical solution to solve energy supply is to adopt microbial cocultivation or cellular nucleoside triphosphate regeneration. This review focused on the sources, preparation methods, biological activities of OBG, and the cultivation methods and applications of microbial cocultivation and fermentation. We also reviewed the preparation methods of other functional oligosaccharides, such as sialylated oligosaccharides, β-nicotinamide mononucleotide, and α-galacto-oligosaccharides.
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http://dx.doi.org/10.1016/bs.aambs.2021.02.002DOI Listing
May 2021

Novel Mitochondria-Targeting and Naphthalimide-based Fluorescent Probe for Detecting HClO in Living Cells.

ACS Omega 2021 Jun 26;6(22):14399-14409. Epub 2021 May 26.

School of Pharmacy, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, PR China.

As a key reactive oxygen species (ROS), hypochlorous acid (HClO) plays an important role in many physiological and pathological processes. The mitochondria-targeting probes for the highly sensitive detection of HClO are desirable. In present work, we designed and synthesized an original mitochondria-localizing and turn-on fluorescent probe for detecting HClO. 4-Aminonaphthalimide was employed as the fluorescent section, the (2-aminoethyl)-thiourea unit was utilized as a typical sensing unit, and the quaternized pyridinium moiety was used as a mitochondria-targeted localization group. When HClO was absent, the probe showed weak fluorescence. In the existence of HClO, the probe revealed a blue fluorescence. Moreover, the turn-on fluorescent probe was able to function in a broad pH scope. There was an excellent linearity between the fluorescence emission intensity at 488 nm and the concentrations of HClO in the range of 5.0 × 10 to 2.5 × 10 mol·L. Additionally, the probe had almost no cell toxicity and possessed an excellent mitochondria-localizing capability. Furthermore, the probe was able to image HClO in mitochondria of living PC-12 cells. The above remarkable properties illustrated that the probe was able to determine HClO in mitochondria of living cells.
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http://dx.doi.org/10.1021/acsomega.1c01271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190919PMC
June 2021

Bandgap Engineering of an Aryl-Fused Tetrathianaphthalene for Visible-Blind Organic Field-Effect Transistors.

Front Chem 2021 28;9:698246. Epub 2021 May 28.

Tianjin Key Laboratory of Molecular Optoelectronic Sciences, Department of Chemistry, School of Science, Tianjin University and Collaborative Innovation Center of Chemical Science and Engineering, Tianjin, China.

Stability problem of organic semiconductors (OSCs) because of photoabsorption has become a major barrier to large scale applications in organic field-effect transistors (OFETs). It is imperative to design OSCs which are insensitive to visible and near-infrared (VNIR) light to obtain both environmental and operational stability. Herein, taking a 2,3,8,9-tetramethoxy [1,4]benzodithiino[2,3-b][1,4]benzodithiine (TTN2) as an example, we show that controlling molecular configuration is an effective strategy to tune the bandgaps of OSCs for visible-blind OFETs. TTN2 adopts an armchair-like configuration, which is different from the prevailing planar structure of common OSCs. Because of the large bandgap, TTN2 exhibits no photoabsorption in the VNIR region and OFETs based on TTN2 show high environmental stability. The devices worked well after being stored in ambient air, (i.e. in the presence of oxygen and water) and light for over two years. Moreover, the OFETs show no observable response to light irradiation from 405-1,020 nm, which is also favorable for high operational stability.
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http://dx.doi.org/10.3389/fchem.2021.698246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193678PMC
May 2021

Analysis of the efficacy and safety of iodine-125 seeds implantation in the treatment of patients with inoperable early-stage non-small cell lung cancer.

J Contemp Brachytherapy 2021 Jun 18;13(3):347-357. Epub 2021 May 18.

Department of Oncology, Hebei General Hospital, Shijiazhuang, Hebei, China.

Purpose: To evaluate the efficacy and safety of iodine-125 (I) seeds implantation for inoperable early-stage non-small cell lung cancer (NSCLC).

Material And Methods: PubMed, Cochrane Library, Embase, China Biology Medicine disc (CBM), China National Knowledge Infrastructure (CNKI), and Wanfang Data were searched from inception until April 2020. Data were collected concerning overall survival, short-term efficacy, and complications. Meta-analysis was performed using R software (version 3.6.3).

Results: Nine studies involving 308 patients were included. Meta-analysis showed that the 1-, 2-, and 3-year survival rates were 0.98% (95% CI: 0.95-0.99%), 0.83% (95% CI: 0.77-0.89%), and 0.65% (95% CI: 0.55-0.75%), respectively; short-term local control rate (LCR) and effective rates were 0.99% (95% CI: 0.98-1.00%) and 0.92% (95% CI: 0.83-0.98%), respectively; 1-, 2-, and 3-year LCRs were 0.96% (95% CI: 0.83-1.00%), 0.94% (95% CI: 0.85-0.99%), and 0.95% (95% CI: 0.76-1.00%), respectively. Sub-group analysis of the prescribed dose found that when the prescribed dose was > 120 Gy, short-term efficacy and 1-year LCR were increased significantly ( 0.01). The incidence of bleeding, pneumothorax, and radiation lung injury was 0.14% (95% CI: 0.07-0.21%), 0.19% (95% CI: 0.11-0.28%), and 0.00% (95% CI: 0.00-0.03%), respectively. Two studies involving 106 patients compared I seeds combined with chemotherapy versus chemotherapy alone for NSCLC. Results showed that compared with chemotherapy alone, I seeds combined with chemotherapy could improve short-term LCR (RR = 1.34, 95% CI: 1.09-1.65%, = 0.005) and short-term effective rate (RR = 1.49, 95% CI: 1.14-1.96%, = 0.004).

Conclusions: I seeds implantation is safe and effective approach for the treatment of inoperable early-stage NSCLC, but high-quality clinical research is still needed to further confirm the findings.
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http://dx.doi.org/10.5114/jcb.2021.106241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170524PMC
June 2021

The Last Chance Saloon.

Front Cell Dev Biol 2021 14;9:671297. Epub 2021 May 14.

Center for Genomic Integrity, Institute for Basic Science, Ulsan, South Korea.

Accurate chromosome segregation requires the removal of all chromatin bridges, which link chromosomes before cell division. When chromatin bridges fail to be removed, cell cycle progression may halt, or cytokinesis failure and ensuing polyploidization may occur. Conversely, the inappropriate severing of chromatin bridges leads to chromosome fragmentation, excessive genome instability at breakpoints, micronucleus formation, and chromothripsis. In this mini-review, we first describe the origins of chromatin bridges, the toxic processing of chromatin bridges by mechanical force, and the TREX1 exonuclease. We then focus on the abscission checkpoint (NoCut) which can confer a transient delay in cytokinesis progression to facilitate bridge resolution. Finally, we describe a recently identified mechanism uncovered in where the conserved midbody associated endonuclease LEM-3/ANKLE1 is able to resolve chromatin bridges generated by various perturbations of DNA metabolism at the final stage of cell division. We also discuss how LEM-3 dependent chromatin bridge resolution may be coordinated with abscission checkpoint (NoCut) to achieve an error-free cleavage, therefore acting as a "last chance saloon" to facilitate genome integrity and organismal survival.
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http://dx.doi.org/10.3389/fcell.2021.671297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160109PMC
May 2021

Sublobar resection with intraoperative brachytherapy versus sublobar resection alone for early-stage non-small-cell lung cancer: a meta-analysis.

Interact Cardiovasc Thorac Surg 2021 Aug;33(3):377-384

Department of Oncology, Hebei General Hospital, Shijiazhuang, Hebei, China.

:

Objectives: The purpose of this study was to compare the clinical outcomes for sublobar resection (SR) or SR plus intraoperative brachytherapy (SRB) for clinical stage I non-small-cell lung cancer.

Methods: A systematic search was performed in the EMBASE, PubMed and Cochrane Library databases to identify related studies comparing SR to SRB. Data were collected on local recurrence (LR) as a primary outcome and regional or distant recurrence, overall survival and disease-free survival (DFS) as secondary outcomes. Meta-analysis was carried out using Stata 12.0.

Results: A total of 476 patients received SRB, and 617 received SR across 5 studies. Meta-analysis of LR, regional or distant recurrence, overall survival and disease-free survival rates showed no significant difference between SRB and SR groups. However, when biologically effective dose (BED) was >100 Gy, LR rate was lower in the SRB group than in the SR group (Relative risk [RR] = 0.143, 95% confidence interval [CI]: 0.051-0.397) (p < 0.001). When BED was <100 Gy, no significant difference was found in LR rate between SRB and SR groups (SRB versus SR: RR = 1.132, 95%CI: 0.704-1.821) (p = 0.608).

Conclusions: Intraoperative brachytherapy was not associated with reduced risk of regional or distant metastasis or improved outcomes for patients with clinical stage I non-small-cell lung cancer; however, it might reduce the LR rate when BED was >100 Gy.
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http://dx.doi.org/10.1093/icvts/ivab097DOI Listing
August 2021

A Modified Method to Isolate Circulating Tumor Cells and Identify by a Panel of Gene Mutations in Lung Cancer.

Technol Cancer Res Treat 2021 Jan-Dec;20:1533033821995275

Department of Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.

The CellSearch system is the only FDA approved and successful used detection technology for circulating tumor cells(CTCs). However, the process for identification of CTCs by CellSearch appear to damage the cells, which may adversely affects subsequent molecular biology assays. We aimed to explore and establish a membrane-preserving method for immunofluorescence identification of CTCs that keeping the isolated cells intact. 98 patients with lung cancer were enrolled, and the efficacy of clinical detection of CTCs was examined. Based on the CellSearch principle, we optimized an anti-EpCAM antibody and improved cell membrane rupture. A 5 ml peripheral blood sample was used to enrich CTCs with EpCAM immunomagnetic beads. Fluorescence signals were amplified with secondary antibodies against anti-EpCAM antibody attached on immunomagnetic beads. After identifying CTCs, single CTCs were isolated by micromanipulation. To confirm CTCs, genomic DNA was extracted and amplified at the single cell level to sequence 72 target genes of lung cancer and analyze the mutation copy number variations (CNVs) and gene mutations. A goat anti-mouse polyclonal antibody conjugated with Dylight 488 was selected to stain tumor cells. We identified CTCs based on EpCAM+ and CD45+ cells to exclude white blood cells. In the 98 lung cancer patients, the detection rate of CTCs (≥1 CTC) per 5 ml blood was 87.76%, the number of detections was 1-36, and the median was 2. By sequencing 72 lung cancer-associated genes, we found a high level of CNVs and gene mutations characteristic of tumor cells. We established a new CTCs staining scheme that significantly improves the detection rate and allows further analysis of CTCs characteristics at the genetic level.
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http://dx.doi.org/10.1177/1533033821995275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155778PMC
May 2021

Quantifying the dynamics of viral recombination during free virus and cell-to-cell transmission in HIV-1 infection.

Virus Evol 2021 Jan 22;7(1):veab026. Epub 2021 Mar 22.

Department of Basic Science, New York University College of Dentistry, 921 Schwartz Building, 345 East 24th Street, New York, NY 10010-9403, USA.

Recombination has been shown to contribute to human immunodeficiency virus-1 (HIV-1) evolution , but the underlying dynamics are extremely complex, depending on the nature of the fitness landscapes and of epistatic interactions. A less well-studied determinant of recombinant evolution is the mode of virus transmission in the cell population. HIV-1 can spread by free virus transmission, resulting largely in singly infected cells, and also by direct cell-to-cell transmission, resulting in the simultaneous infection of cells with multiple viruses. We investigate the contribution of these two transmission pathways to recombinant evolution, by applying mathematical models to experimental data on the growth of fluorescent reporter viruses under static conditions (where both transmission pathways operate), and under gentle shaking conditions, where cell-to-cell transmission is largely inhibited. The parameterized mathematical models are then used to extrapolate the viral evolutionary dynamics beyond the experimental settings. Assuming a fixed basic reproductive ratio of the virus (independent of transmission pathway), we find that recombinant evolution is fastest if virus spread is driven only by cell-to-cell transmission and slows down if both transmission pathways operate. Recombinant evolution is slowest if all virus spread occurs through free virus transmission. This is due to cell-to-cell transmission 1, increasing infection multiplicity; 2, promoting the co-transmission of different virus strains from cell to cell; and 3, increasing the rate at which point mutations are generated as a result of more reverse transcription events. This study further resulted in the estimation of various parameters that characterize these evolutionary processes. For example, we estimate that during cell-to-cell transmission, an average of three viruses successfully integrated into the target cell, which can significantly raise the infection multiplicity compared to free virus transmission. In general, our study points towards the importance of infection multiplicity and cell-to-cell transmission for HIV evolution.
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http://dx.doi.org/10.1093/ve/veab026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117450PMC
January 2021

Expression Profile of Long Noncoding RNAs and Circular RNAs in Mouse C3H10T1/2 Mesenchymal Stem Cells Undergoing Myogenic and Cardiomyogenic Differentiation.

Stem Cells Int 2021 30;2021:8882264. Epub 2021 Apr 30.

Department of Cell Biology, Medical College of Soochow University, Soochow University, Ren Ai Road 199, Suzhou Industrial Park, Suzhou 215123, China.

Background: Currently, a heterogeneous category of noncoding RNAs (ncRNA) that directly regulate the expression or function of protein-coding genes is shown to have an effect on the fate decision of stem cells. However, the detailed regulatory roles of ncRNAs in myogenic and cardiomyogenic differentiation of mouse C3H10T1/2 mesenchymal stem cells (MSCs) are far from clear.

Methods: In this study, 5-azacytidine- (5-AZA-) treated C3H10T1/2 cells were differentiated into myocyte-like and cardiomyocyte-like cells. Next, ncRNA associated with myogenic and cardiomyogenic differentiation was identified using high-throughput RNA sequencing (RNA-seq) data. Bioinformatics analysis was conducted to identify the differentially expressed ncRNAs and the related signaling pathways.

Results: Myotube-like structure was formed after 5-AZA treatment of C3H10T1/2 cells. In addition, myogenic and cardiomyogenic differentiation-related genes like , , , and were upregulated significantly after the 5-AZA treatment. Totally, 1538 differentially expressed lncRNAs and 3398 differentially expressed mRNAs were identified, including 1175 upregulated and 363 downregulated lncRNAs and 2429 upregulated and 969 downregulated mRNAs. In addition, 46 differentially expressed circRNAs were identified, including 25 upregulated and 21 downregulated circRNAs. Moreover, the differentially expressed mRNAs were enriched into 5 significant pathways, including those for focal adhesion, ECM-receptor interaction, PI3K-AKT signaling pathway, PPAR signaling pathway, and Tyrosine metabolism.

Conclusions: A systematic view of the expression of ncRNAs in myogenic and cardiomyogenic differentiation of MSCs was provided in the study.
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http://dx.doi.org/10.1155/2021/8882264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105102PMC
April 2021

Association of intracranial vessel wall enhancement and cerebral hemorrhage in moyamoya disease: a high-resolution magnetic resonance imaging study.

J Neurol 2021 May 6. Epub 2021 May 6.

Department of Radiology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, 100853, China.

Background And Purpose: This study aimed to investigate the enhancement characteristics of vessel wall in patients with moyamoya disease (MMD) using 3D high-resolution magnetic resonance (MR) imaging and their relationship with initial and recurrent intracranial hemorrhage.

Methods: Consecutive patients with MMD were retrospectively analyzed and classified as intracranial hemorrhagic and non-hemorrhagic groups according to the CT or MR images. The clinical features and vessel wall characteristics were compared between the two groups. Logistic regression was performed to relate the vessel wall characteristics to the initial hemorrhage in MMD patients. Patients in hemorrhagic group were followed up after surgery to evaluate the relationship between vessel wall characteristics and recurrent hemorrhage.

Results: A total of 507 MMD patients including 79 hemorrhagic and 428 non-hemorrhagic MMD patients were recruited in the study. We found that hemorrhagic group had more patients with vessel wall enhancements (40.5% vs. 25.7%, p = 0.009) and more eccentric enhanced lesions (17.7% vs. 6.5%, p = 0.001) compared to those in non-hemorrhage group and vessel wall enhancements were independently associated with ipsilateral initial hemorrhage after adjusted for clinical factors (OR = 1.99, CI 1.20-3.28, p = 0.007). Furthermore, three recurrent intracranial hemorrhagic episodes in the present study were all observed in MMD patients with vessel wall enhancement during the long-term follow-up after surgery.

Conclusions: Wall enhancement of intracranial vessels was significantly associated with intracranial hemorrhage in MMD patients. Our findings suggest that vessel wall enhancement may serve as a marker of intracranial hemorrhage.
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http://dx.doi.org/10.1007/s00415-021-10587-6DOI Listing
May 2021

3D MRI Reconstruction Based on 2D Generative Adversarial Network Super-Resolution.

Sensors (Basel) 2021 Apr 23;21(9). Epub 2021 Apr 23.

School of Information, Kochi University of Technology, Kami, Kochi 782-8502, Japan.

The diagnosis of brain pathologies usually involves imaging to analyze the condition of the brain. Magnetic resonance imaging (MRI) technology is widely used in brain disorder diagnosis. The image quality of MRI depends on the magnetostatic field strength and scanning time. Scanners with lower field strengths have the disadvantages of a low resolution and high imaging cost, and scanning takes a long time. The traditional super-resolution reconstruction method based on MRI generally states an optimization problem in terms of prior information. It solves the problem using an iterative approach with a large time cost. Many methods based on deep learning have emerged to replace traditional methods. MRI super-resolution technology based on deep learning can effectively improve MRI resolution through a three-dimensional convolutional neural network; however, the training costs are relatively high. In this paper, we propose the use of two-dimensional super-resolution technology for the super-resolution reconstruction of MRI images. In the first reconstruction, we choose a scale factor of 2 and simulate half the volume of MRI slices as input. We utilize a receiving field block enhanced super-resolution generative adversarial network (RFB-ESRGAN), which is superior to other super-resolution technologies in terms of texture and frequency information. We then rebuild the super-resolution reconstructed slices in the MRI. In the second reconstruction, the image after the first reconstruction is composed of only half of the slices, and there are still missing values. In our previous work, we adopted the traditional interpolation method, and there was still a gap in the visual effect of the reconstructed images. Therefore, we propose a noise-based super-resolution network (nESRGAN). The noise addition to the network can provide additional texture restoration possibilities. We use nESRGAN to further restore MRI resolution and high-frequency information. Finally, we achieve the 3D reconstruction of brain MRI images through two super-resolution reconstructions. Our proposed method is superior to 3D super-resolution technology based on deep learning in terms of perception range and image quality evaluation standards.
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http://dx.doi.org/10.3390/s21092978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122986PMC
April 2021

Metabolic profiles of oligosaccharides derived from four microbial polysaccharides by faecal inocula from type 2 diabetes patients.

Int J Food Sci Nutr 2021 Apr 17:1-12. Epub 2021 Apr 17.

The Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, China.

digestion of curdlan oligosaccharides (COSs), pullulan oligosaccharides (POSs), xanthan gum oligosaccharides (XGOSs) and gellan gum oligosaccharides (GGOSs) was investigated. These four oligosaccharides showed resistance to simulated saliva and gastric and small intestinal fluid. In further fermentation with faecal microbiota from healthy subjects and type 2 diabetes (T2D) patients, COS fermentation significantly increased the abundance of spp. and spp. and the production of short-chain fatty acids in healthy and T2D groups. Digestion of XGOS enhanced the growth of the subgroup and significantly increased butyric acid production in healthy and T2D groups. Sole fermentation with COS, POS, XGOS and GGOS exhibited different metabolic profiles between healthy and T2D groups, and more small molecule polyols were produced in the T2D group than in the healthy group. This study provides a novel perspective on the reconstruction of gut microbiota and metabolism by POS, COS, GGOS and XGOS intervention.
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http://dx.doi.org/10.1080/09637486.2021.1908964DOI Listing
April 2021

Low expression of BTN3A3 indicates poor prognosis and promotes cell proliferation, migration and invasion in non-small cell lung cancer.

Ann Transl Med 2021 Mar;9(6):478

No. 2 Department of Thoracic Surgery, Beijing Tuberculosis and Thoracic Tumor Research Institute/Beijing Chest Hospital, Capital Medical University, Beijing, China.

Background: The butyrophilin (BTN) family has many members with diverse functions related to immunomodulation, initiation and progression of tumors. BTN3A3 belongs to the BTN family, and exploring its expression and correlation with the prognosis of non-small cell lung cancer (NSCLC) patients has great clinical significance.

Methods: Clinical specimens were used to detect BTN3A3 expression. Small interfering RNA (siRNA) was used to knock down BTN3A3 and analyze the proliferative, migratory and invading ability of the transfected NSCLC cells. Multiplex immunofluorescence staining was used to detect the expression of BTN3A3 protein in the tumor microenvironment (TME). We analyzed the relationship between the expression of BTN3A3 and the clinicopathological features and prognosis of NSCLC patients.

Results: The expression of BTN3A3 in NSCLC tissues was significantly lower than in adjacent tissues, and patients with low expression of BTN3A3 had late clinical stages and lower degree of tumor differentiation. Knocking down BTN3A3 promoted the proliferation, migration and invasion of NSCLC. In the TME, the density of BTN3A3+ tumor cells positively correlated with the density of CD8+ T cells, and the patients with low expression of BTN3A3 had poor overall survival (OS).

Conclusions: Changes in the BTN3A3 expression level may play a potential key role in the carcinogenesis and development of NSCLC. Patients with low expression of BTN3A3 showed a more aggressive and invasive phenotype and a lower level of CD8+ T-cell infiltration, which may be an important factor affecting the OS of NSCLC patients.
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http://dx.doi.org/10.21037/atm-21-163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039694PMC
March 2021

Identification of a Metastasis-Associated Gene Signature of Clear Cell Renal Cell Carcinoma.

Front Genet 2020 4;11:603455. Epub 2021 Feb 4.

He'nan Provincial Key Laboratory of Kidney Disease and Immunology, Department of Nephrology, He'nan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, China.

Clear cell renal cell carcinoma (ccRCC) is one of the most frequent pathological subtypes of kidney cancer, accounting for ~70-75%, and the major cause of mortality is metastatic disease. The difference in gene expression profiles between primary ccRCC tumors and metastatic tumors has not been determined. Thus, we report integrated genomic and transcriptomic analysis for identifying differentially expressed genes (DEGs) between primary and metastatic ccRCC tumors to understand the molecular mechanisms underlying the development of metastases. The microarray datasets GSE105261 and GSE85258 were obtained from the Gene Expression Omnibus (GEO) database, and the R package limma was used for DEG analyses. In summary, the results described herein provide important molecular evidence that metastatic ccRCC tumors are different from primary tumors. Enrichment analysis indicated that the DEGs were mainly enriched in ECM-receptor interaction, platelet activation, protein digestion, absorption, focal adhesion, and the PI3K-Akt signaling pathway. Moreover, we found that DEGs associated with a higher level of tumor immune infiltrates and tumor mutation burden were more susceptible to poor prognosis of ccRCC. Specifically, our study indicates that seven core genes, namely the collagen family (COL1A2, COL1A1, COL6A3, and COL5A1), DCN, FBLN1, and POSTN, were significantly upregulated in metastatic tumors compared with those in primary tumors and, thus, potentially offer insight into novel therapeutic and early diagnostic biomarkers of ccRCC.
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http://dx.doi.org/10.3389/fgene.2020.603455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889952PMC
February 2021

Electrohydrodynamic 3D Printing Scaffolds for Repair of Achilles Tendon Defect in Rats.

Tissue Eng Part A 2021 Mar 30. Epub 2021 Mar 30.

Department of Cell Biology, Medical College of Soochow University, Soochow University, Suzhou, China.

Tissue engineering (TE) studies for Achilles tendon (AT) defects are a difficult and popular field in orthopedic medical practice. In this study, we applied electrohydrodynamic three-dimensional (3D) printing technology to construct scaffolds made of poly-(ɛ-ɛ-caprolactone) (PCL) and Pluronic F127 (F127) with different mass-volume ratios. The fibers and porous capabilities of the scaffolds were controlled using this technology. We found that F127 improved the hydrophilicity and degradation of PCL . The PCL scaffolds with 5% F127 were mostly favorable for cell adhesion and growth, suggesting that the scaffolds had good biocompatibility . Scaffolds with 5% F127 seeded with C3H10T1/2 cells were transplanted into AT defects in rats. A histological analysis indicated that the TE scaffolds were beneficial for the accumulation and arrangement of collagen fibers. Thus, this study provides fundamental experimental data for future clinical applications regarding TE for ATs.
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http://dx.doi.org/10.1089/ten.TEA.2020.0290DOI Listing
March 2021

Therapeutic potential of TNFα inhibitors in chronic inflammatory disorders: Past and future.

Genes Dis 2021 Jan 3;8(1):38-47. Epub 2020 Mar 3.

Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

In the past 20 years, patients with rheumatoid arthritis (RA), Crohn's disease (CD), and other immune diseases have witnessed the impact of a great treatment advance with the availability of biological TNFα inhibitors. With 5 approved anti-TNFα biologics on the market and soon available biosimilars, patients have more treatment options and have benefited from understanding the biology of TNFα. Nevertheless, many unmet needs remain for people living with TNFα-related diseases, namely some side effects and tolerance of current anti-TNFα biologics and resistance to therapies. Furthermore, common diseases such as osteoarthritis and back/neck pain may respond to anti-TNFα therapies at early onset of symptoms. Development of new TNFα inhibitors focusing on TNFR1 specific inhibitors, preferably small molecules that can be delivered orally, is much needed.
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http://dx.doi.org/10.1016/j.gendis.2020.02.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859422PMC
January 2021

DP from Euphorbia fischeriana S. mediated apoptosis in leukemia cells via the PI3k/Akt signaling pathways.

J Ethnopharmacol 2021 Oct 30;279:113889. Epub 2021 Jan 30.

Qiqihaer Medical University, Heilongjiang Qiqihaer, China. Electronic address:

Ethnopharmacological Relevance: Euphorbia fischeriana S. (E. fischeriana) is a classic Chinese herb with toxicity that is mainly used for cancer treatment and in insect repellent, anti-inflammatory and anti-edema applications (Liu et al., 2001). 12-Deoxyphorbol13-palmitate (DP), a tetracyclic diterpene monomer compound, was extracted from the roots of E. fischeriana by our research groups.

Aim: Previous studies found that DP could inhibit the proliferation of leukemia cells in vitro. However, the underlying mechanism of DP in leukemia is unknown. Hence, DP's pharmacological effect on leukemia cells was investigated in this study.

Materials And Methods: DP was obtained from the Natural Medicine Chemistry Laboratory of Qiqihaer Medical University. In vitro, K562 cells and HL60 cells were incubated with DP or DP combined with LY294002 at different concentrations. Cell proliferation and apoptosis were detected by the relevant experimental methods. In vivo, nude mouse xenograft models were established by injecting K562 cells. DP was intraperitoneally administered to observe the influence on the growth of transplanted tumors. Gene detection and immunoblot analysis were performed to validate the mechanisms.

Results: The cell counting kit-8 (CCK-8) assay proved that DP inhibited the growth of K562 and HL60 cells in a time- or dose-dependent manner. At 12 h, DP could induce apoptosis by Annexin V-FITC/propidium iodide (PI) dual labeling, loss of mitochondrial membrane potential (MMP), intracellular reactive oxygen species (ROS), acridine orange/ethidium bromide (AO/EB) staining and transmission electron microscopy (TEM) observation in K562 or HL60 cells. Furthermore, in an assay of gene and protein expression, we found that DP could downregulate the gene and protein expression levels of Bcl-2, upregulate the gene and protein expression levels of Bax and Bim, and downregulate the protein expression levels of PI3k, p-Akt, and p-FoxO3a. Moreover, the effects of DP on proliferation and apoptosis in K562 cells were enhanced by LY294002. Then, we tested the antitumor effects of DP in vivo. Nude mouse xenograft models were established by subcutaneously injecting K562 cells. We found that tumor volume was significantly decreased in DP-treated xenograft nude mice. Morphologic changes, apoptosis degree, and related gene and protein expression levels in transplanted tumor tissue of DP-treated nude mice were assessed by different experimental methods.

Conclusions: The in vivo and in vitro experimental results indicated that DP might inhibit the proliferation and induce the apoptosis of leukemia cells, which might be a result of suppressing the PI3k/Akt signaling pathways.
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http://dx.doi.org/10.1016/j.jep.2021.113889DOI Listing
October 2021

The effectiveness and prognostic factors of radioactive iodine-125 seed implantation for the treatment of cervical lymph node recurrence of esophageal squamous cell carcinoma after external beam radiation therapy.

J Contemp Brachytherapy 2020 Dec 16;12(6):579-585. Epub 2020 Dec 16.

Department of Oncology, Hebei General Hospital, Shijiazhuang, Hebei, China.

Purpose: To analyze factors influencing the efficacy of I seed implantation in the treatment of in-field cervical lymph node recurrence of esophageal squamous cell carcinoma (ESCC) after external beam radiation therapy.

Material And Methods: We conducted a retrospective review of 36 patients with in-field cervical metastatic lymph nodes recurrence of esophageal squamous cell carcinoma (CML-ESCC) after external beam radiation therapy treatment, who underwent I seed implantation in our department from 2013 to 2019. Previous cumulative external irradiation dose ranged from 20 to 66 Gy (median, 60 Gy). The post-implant efficacy was evaluated by response evaluation criteria in solid tumors (RECIST) version 1.1, and an adverse event was evaluated by the Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Score (EORTC). COX proportional hazards model was used to analyze risk factors affecting effectiveness.

Results: Among 36 patients, 31 patients (86.1%) received fluorouracil-based chemotherapy (1-6 cycles) after I seed implantation. Local control rates at 3, 6, 12, and 24 months after implantation were 51%, 30%, 30%, and 18%, respectively, with a median of 9 months (95% CI: 6.106-11.894); survival rates after 3, 6, 12, and 24 months were 55%, 41%, 22%, and 22%, respectively, with a median of 8 months (95% CI: 5.753-10.247). Multivariate analysis showed that D and short-term efficacy were independent factors related to local control and survival rate ( = 0.005, < 0.001, 0.010, < 0.001). There were 2 cases (5.6%) with grade 1 skin toxicity, 1 case (2.8%) with grade 4 skin toxicity, 3 cases (8.3%) with grade 1 mucosal ulcer, and 3 cases (8.3%) with grade 1 xerostomia.

Conclusions: I seed implantation as an effective salvage treatment shows definite efficacy and safety for patients with in-field cervical lymph node recurrence of ESCC after external beam radiation therapy.
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http://dx.doi.org/10.5114/jcb.2020.101691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787212PMC
December 2020

MicroRNA-199-3p up-regulation enhances chondrocyte proliferation and inhibits apoptosis in knee osteoarthritis via DNMT3A repression.

Inflamm Res 2021 Feb 12;70(2):171-182. Epub 2021 Jan 12.

Department of Orthopaedics, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu Province, People's Republic of China.

Aim: Studies have pivoted on the position of microRNAs (miRNAs) in knee osteoarthritis (KOA) but not the more specific function of miR-199-3p. Thus, this study is to uncover the mechanism of miR-199-3p in KOA.

Methods: Rats KOA models were established by modified Hulth method. miR-199-3p expression was observed in cartilage of KOA rats. The binding sites of miR-199-3p were predicted by bioinformatics analysis and the potential interaction between DNA methyltransferase 3A (DNMT3A) and miR-199-3p was verified by dual-luciferase reporter gene assay. Rats were injected with miR-199-3p agomir or antagomir and DNMT3A siRNA into the knee joint. Inflammatory response factors in serum and cartilage tissues, cell apoptosis, and pathological status of cartilage tissues were detected. Chondrocytes were isolated from KOA cartilages and treated with miR-199-3p mimic or inhibitor and DNMT3A siRNA. Chondrocyte proliferation and apoptosis were detected.

Results: miR-199-3p expression was suppressed in cartilage of KOA rats. Dual-luciferase reporter gene assay proved that a miR-199-3p-binding site was located in the 3'UTR of DNMT3A mRNA. Inflammation, chondrocyte apoptosis and cartilage pathological changes were improved by miR-199-3p agomir but aggravated by miR-199-3p antagomir. The effects of miR-199-3p antagomir on KOA rats were partially reversed by DNMT3A siRNA. miR-199-3p mimic or DNMT3A siRNA decreased KOA chondrocytes apoptosis and promoted proliferation. miR-199-3p inhibitor showed the opposite functions to miR-199-3p mimic. The effects of miR-199-3p inhibitor on chondrocytes were reversed by DNMT3A siRNA.

Conclusion: This study highlights that miR-199-3p up-regulation or down-regulation of DNMT3A induces chondrocyte proliferation and inhibits apoptosis in KOA, which may widen our eyes to treat patients with KOA.
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http://dx.doi.org/10.1007/s00011-020-01430-1DOI Listing
February 2021

Th1 cytokine interferon gamma improves response in HER2 breast cancer by modulating the ubiquitin proteasomal pathway.

Mol Ther 2021 04 5;29(4):1541-1556. Epub 2021 Jan 5.

Clinical Science & Immunology Program, H. Lee Moffitt Cancer Center, Tampa, FL, USA; Department of Breast Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA. Electronic address:

HER2 breast cancer (BC) remains a significant problem in patients with locally advanced or metastatic BC. We investigated the relationship between T helper 1 (Th1) immune response and the proteasomal degradation pathway (PDP), in HER2-sensitive and -resistant cells. HER2 overexpression is partially maintained because E3 ubiquitin ligase Cullin5 (CUL5), which degrades HER2, is frequently mutated or underexpressed, while the client-protective co-chaperones cell division cycle 37 (Cdc37) and heat shock protein 90 (Hsp90) are increased translating to diminished survival. The Th1 cytokine interferon (IFN)-γ caused increased CUL5 expression and marked dissociation of both Cdc37 and Hsp90 from HER2, causing significant surface loss of HER2, diminished growth, and induction of tumor senescence. In HER2-resistant mammary carcinoma, either IFN-γ or Th1-polarizing anti-HER2 vaccination, when administered with anti-HER2 antibodies, demonstrated increased intratumor CUL5 expression, decreased surface HER2, and tumor senescence with significant therapeutic activity. IFN-γ synergized with multiple HER2-targeted agents to decrease surface HER2 expression, resulting in decreased tumor growth. These data suggest a novel function of IFN-γ that regulates HER2 through the PDP pathway and provides an opportunity to impact HER2 responses through anti-tumor immunity.
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http://dx.doi.org/10.1016/j.ymthe.2020.12.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058490PMC
April 2021

Effects of chemical modification on physicochemical properties and adsorption behavior of sludge-based activated carbon.

J Environ Sci (China) 2021 Feb 17;100:340-352. Epub 2020 Aug 17.

School of Environment Studies, China University of Geosciences, Wuhan 430074, China. Electronic address:

This study aimed to explore the adsorption performance of sludge-based activated carbon (SBC) towards dissolved organic matters (DOMs) removal from sewage, and investigated the modification effect of different types of chemicals on the structure of synthesized SBC. Waste activated sludge (WAS) was used as a carbon source, and HCl, HNO, and NaOH were used as different types of chemicals to modify the SBC. With the aid of chemical activation, the modified SBC showed higher adsorption performances on DOMs removal with maximum adsorption of 29.05 mg/g and second-order constant (k) of 0.1367 (L/mol/sec) due to the surface elution of ash and minerals by chemicals. The surface elemental composition of MSBC suggested that the content of C-C and C-O functional groups on the surface of modified sludge-based activated carbon (MSBC) played an important role on the adsorption capacities of MSBC towards DOMs removal in sewage. Additionally, the residual molecular weight of DOMs in sewage was investigated using a 3-dimension fluorescence excitation-emission matrix (3D-EEM) and high-performance size exclusion chromatography (HP-SEC). Results showed that the chemical modification significantly improved the adsorption capacity of MSBC on humic acids (HA) and aromatic proteins (APN), and both of NaOH-MSBC and HCl-MSBC were effective for a wide range of different AMW DOMs removal from sewage, while the HNO-MSBC exhibited poorly on AMW organics of 2,617 Da and 409 Da due to the reducing content of macropore. In brief, this study provides reference values for the impact of the chemicals of the activation stage before the SBCs application.
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http://dx.doi.org/10.1016/j.jes.2020.08.005DOI Listing
February 2021
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