Publications by authors named "Shao-Jie Zhang"

10 Publications

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Research progress of dual inhibitors targeting crosstalk between histone epigenetic modulators for cancer therapy.

Eur J Med Chem 2021 Jun 1;222:113588. Epub 2021 Jun 1.

School of Pharmacy, Xinxiang Medical University, 453003, Xinxiang, Henan Province, PR China. Electronic address:

Abnormal epigenetics is a critical hallmark of human cancers. Anticancer drug discovery directed at histone epigenetic modulators has gained impressive advances with six drugs available for cancer therapy and numerous other candidates undergoing clinical trials. However, limited therapeutic profile, drug resistance, narrow safety margin, and dose-limiting toxicities pose intractable challenges for their clinical utility. Because histone epigenetic modulators undergo intricate crosstalk and act cooperatively to shape an aberrant epigenetic profile, co-targeting histone epigenetic modulators with a different mechanism of action has rapidly emerged as an attractive strategy to overcome the limitations faced by the single-target epigenetic inhibitors. In this review, we summarize in detail the crosstalk of histone epigenetic modulators in regulating gene transcription and the progress of dual epigenetic inhibitors targeting this crosstalk.
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http://dx.doi.org/10.1016/j.ejmech.2021.113588DOI Listing
June 2021

Design, synthesis, and biological evaluation of novel dual inhibitors targeting lysine specific demethylase 1 (LSD1) and histone deacetylases (HDAC) for treatment of gastric cancer.

Eur J Med Chem 2021 Aug 25;220:113453. Epub 2021 Apr 25.

School of Pharmacy, Xinxiang Medical University, Xinxiang, Henan, 453003, China. Electronic address:

LSD1 and HDAC are physical and functional related to each other in various human cancers and simultaneous pharmacological inhibition of LSD1 and HDAC exerts synergistic anti-cancer effects. In this work, a series of novel LSD1/HDAC bifunctional inhibitors with a styrylpyridine skeleton were designed and synthesized based on our previously reported LSD1 inhibitors. The representative compounds 5d and 5m showed potent activity against LSD1 and HDAC at both molecular and cellular level and displayed high selectivity against MAO-A/B. Moreover, compounds 5d and 5m demonstrated potent antiproliferative activities against MGC-803 and HCT-116 cancer cell lines. Notably, compound 5m showed superior in vitro anticancer potency against a panel of gastric cancer cell lines than ORY-1001 and SP-2509 with IC values ranging from 0.23 to 1.56 μM. Compounds 5d and 5m significantly modulated the expression of Bcl-2, Bax, Vimentin, ZO-1 and E-cadherin, induced apoptosis, reduced colony formation and suppressed migration in MGC-803 cancer cells. In addition, preliminary absorption, distribution, metabolism, excretion (ADME) studies revealed that compounds 5d and 5m showed acceptable metabolic stability in human liver microsomes with minimal inhibition of cytochrome P450s (CYPs). Those results indicated that compound 5m could be a promising lead compound for further development as a therapeutic agent in gastric cancers via LSD1 and HDAC dual inhibition.
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http://dx.doi.org/10.1016/j.ejmech.2021.113453DOI Listing
August 2021

Effects of Surgery Combined with Chemoradiotherapy on Short- and Long-Term Outcomes of Early-Stage Nasopharyngeal Carcinoma.

Cancer Manag Res 2020 25;12:7813-7826. Epub 2020 Aug 25.

Department of Otolaryngology & Head and Neck, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, People's Republic of China.

Objective: The efficacy of surgery as the primary treatment modality for nasopharyngeal carcinoma (NPC) is yet to be clarified. Therefore, we aimed to explore the short- and long-term efficacy of surgery for early-stage NPC.

Methods: We retrospectively evaluated 341 patients diagnosed with early-stage NPC between September 2010 and December 2015. Among them, 58 patients underwent endoscopic nasopharyngectomy combined with chemoradiotherapy, whereas 283 patients underwent conventional chemoradiotherapy. The patients who underwent concurrent chemoradiotherapy or radiotherapy alone were matched to patients who underwent surgery in a 1:2 ratio using propensity score matching to analyze the clinical efficacy of each therapeutic modality. The primary endpoint was survival, and the secondary endpoints were tumor regression rate and reduction in Epstein-Barr virus (EBV)-DNA levels.

Results: After matching, 156 patients were enrolled (58 patients in the surgery group; 98 patients in the non-surgery group). The baseline data of the matched patients had good inter-group comparability (All P>0.05). The surgery group had significantly higher 5-year overall survival (98.30% vs. 91.70%), disease-free survival (98.30% vs. 81.40%), and recurrence-free survival (100.00% vs. 90.10%) rates than did the non-surgery group (All P<0.05). In total, 0 and 14 patients in the surgery and non-surgery groups, respectively, had residual cancer at the end of treatment (P=0.001). All patients in the surgery group tested negative for EBV-DNA, whereas two patients in the non-surgery group tested positive. The incidence of hematologic toxicity during treatment was similar between the two groups (All P>0.05). Still, the incidence of severe oral mucositis was lower in the surgery group than in the non-surgery group (37.9% vs. 54.08%, P=0.051).

Conclusion: Surgery can improve the clearance rate of EB virus and reduce tumor residue. Surgery may be a safe and effective treatment for early NPC.
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http://dx.doi.org/10.2147/CMAR.S262567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457865PMC
August 2020

Genomic regions under selection in the feralization of the dingoes.

Nat Commun 2020 02 3;11(1):671. Epub 2020 Feb 3.

State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.

Dingoes are wild canids living in Australia, originating from domestic dogs. They have lived isolated from both the wild and the domestic ancestor, making them a unique model for studying feralization. Here, we sequence the genomes of 10 dingoes and 2 New Guinea Singing Dogs. Phylogenetic and demographic analyses show that dingoes originate from dogs in southern East Asia, which migrated via Island Southeast Asia to reach Australia around 8300 years ago, and subsequently diverged into a genetically distinct population. Selection analysis identifies 50 positively selected genes enriched in digestion and metabolism, indicating a diet change during feralization of dingoes. Thirteen of these genes have shifted allele frequencies compared to dogs but not compared to wolves. Functional assays show that an A-to-G mutation in ARHGEF7 decreases the endogenous expression, suggesting behavioral adaptations related to the transitions in environment. Our results indicate that the feralization of the dingo induced positive selection on genomic regions correlated to neurodevelopment, metabolism and reproduction, in adaptation to a wild environment.
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http://dx.doi.org/10.1038/s41467-020-14515-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997406PMC
February 2020

Three-dimensional digitizing and anatomic study of lumbar vertebral canal and pedicle in children.

Wideochir Inne Tech Maloinwazyjne 2018 Dec 8;13(4):518-524. Epub 2018 Aug 8.

Teaching and Researching Institute of Human Anatomy, School of Basic Medicine, Hohhot, China.

Introduction: Spinal pedicle screw internal fixation has been widely used in adult spine injury fixation. Due to being in a period of continuous growth and development, the spine of children at different ages shows different characteristics from adults in terms of anatomy, physiological function, and biomechanics. Furthermore, because the pedicle of children is small, has large anatomic variation, and has complex adjacent relationships, the surgical risk is extremely high. How to improve the screwing accuracy is the key to the success of children's pedicle internal fixation. Therefore, applying the concept of digitized and individualized screwing will be of great significance to children's pedicle screwing.

Aim: To investigate the morphologies, development patterns, and aging characteristics of the lumbar vertebral pedicle (LVP) in children aged 6-11 years, and to provide a theoretical basis for screw implantation and related biomechanical studies.

Material And Methods: A total of 60 children aged 6-11 years were selected for the intergroup measurement and statistical analysis of their lumbar diameter, pedicle diameter, screw canal length (SCL), etc.

Results: Generally, the vertebral foramen diameter (ID), sagittal diameter (SD), pedicle width (PW), and SCL as well as the pedicle height (PH) exhibited an increasing trend with age and increasing vertebral sequence among children aged 6-11 years.

Conclusions: By observing the LVP in children using 3D digital reconstruction technology, the morphology of the spinal canal and pedicles at different lumbar segments showed obvious development patterns, and the best treatment protocol should be selected according to the LVP characteristics in clinical applications.
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http://dx.doi.org/10.5114/wiitm.2018.77554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280084PMC
December 2018

[Primary tuberculosis of unilateral vocal cord: two case reports].

Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2013 Sep;48(9):771-2

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September 2013

EEG patterns from acute to chronic stroke phases in focal cerebral ischemic rats: correlations with functional recovery.

Physiol Meas 2013 Apr 22;34(4):423-35. Epub 2013 Mar 22.

Interdisciplinary Division of Biomedical Engineering, the Hong Kong Polytechnic University, Hong Kong.

Monitoring the neural activities from the ischemic penumbra provides critical information on neurological recovery after stroke. The purpose of this study is to evaluate the temporal alterations of neural activities using electroencephalography (EEG) from the acute phase to the chronic phase, and to compare EEG with the degree of post-stroke motor function recovery in a rat model of focal ischemic stroke. Male Sprague-Dawley rats were subjected to 90 min transient middle cerebral artery occlusion surgery followed by reperfusion for seven days (n = 58). The EEG signals were recorded at the pre-stroke phase (0 h), acute phase (3, 6 h), subacute phase (12, 24, 48, 72 h) and chronic phase (96, 120, 144, 168 h) (n = 8). This study analyzed post-stroke seizures and polymorphic delta activities (PDAs) and calculated quantitative EEG parameters such as the alpha-to-delta ratio (ADR). The ADR represented the ratio between alpha power and delta power, which indicated how fast the EEG activities were. Forelimb and hindlimb motor functions were measured by De Ryck's test and the beam walking test, respectively. In the acute phase, delta power increased fourfold with the occurrence of PDAs, and the histological staining showed that the infarct was limited to the striatum and secondary sensory cortex. In the subacute phase, the alpha power reduced to 50% of the baseline, and the infarct progressed to the forelimb cortical region. ADRs reduced from 0.23 ± 0.09 to 0.04 ± 0.01 at 3 h in the acute phase and gradually recovered to 0.22 ± 0.08 at 168 h in the chronic phase. In the comparison of correlations between the EEG parameters and the limb motor function from the acute phase to the chronic phase, ADRs were found to have the highest correlation coefficients with the beam walking test (r = 0.9524, p < 0.05) and De Ryck's test (r = 0.8077, p < 0.05). This study measured EEG activities after focal cerebral ischemia and showed that functional recovery was closely correlated with the neural activities in the penumbra. Longitudinal EEG monitoring at different phases after a stroke can provide information on the neural activities, which are well correlated with the motor function recovery.
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http://dx.doi.org/10.1088/0967-3334/34/4/423DOI Listing
April 2013

[Clinical comparative study on the influence of acupoint sticking therapy in dog days and in non-dog days to the quality of life of allergic rhinitis patients].

Zhongguo Zhen Jiu 2012 Jan;32(1):31-4

School of TCM, Southern Medical University, Guangzhou 510515, Guangdong Province, China.

Objective: To observe and compare the influence of acupoint sticking therapy in dog days and in non-dog days to the quality of life of allergic rhinitis patients.

Methods: Fifty-five cases were divided into group A (the acupoint sticking therapy in dog days group, 28 cases) and group B (the acupoint sticking therapy in non-dog day group, 27 cases) randomly. The acupoint sticking therapy description (Dazhui (GV 14), Fengmen (BL 12), Feishu (BL 13) etc. was used in both groups. Five times of acupoint sticking therapy were given to patients in group A during dog days in 2010, while another 5 times of acupoint sticking therapy were given to patients in group B before the dog days. The Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) was used to evaluate the effects before, after and half a year after treatment.

Results: The scores of behavior problems, nasal symptoms and quality of life in RQLQ of both groups all decreased after treatment (all P < 0.01). The score of emotion reaction of group A in the follow-up period decreased compared with that before treatment (P < 0.05). The scores of non-nasal-or-ocular symptoms, ocular symptoms and emotion reaction after treatment and in the follow-up period all decreased than those before treatment (P < 0.01, P < 0.05). The decreasing degrees of scores of non-nasal-or-ocular symptoms, ocular symptoms, emotion reaction and quality of life after treatment and in the follow-up period in group A were all greater than those in group B (P < 0.01, P < 0.05).

Conclusion: In the same season, both acupoint sticking therapy in dog days and in non-dog dags can improve the symptoms of allergic rhinitis, but the improving degree to quality of life in the method of acupoint sticking in dog days is greater.
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January 2012

Nitric oxide, actin reorganization and vacuoles change are involved in PEG 6000-induced stomatal closure in Vicia faba.

Physiol Plant 2009 May 12;136(1):45-56. Epub 2009 Feb 12.

Key Laboratory of Medicinal Plant Resource and Natural Pharmaceutical Chemistry of Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, China.

Water deficit and the resulting osmotic stress affect stomatal movement. There are two types of signals, hydraulic and chemical signals, involving in the regulation of stomatal behavior responses to osmotic stress. Compared with the chemical signals, little has been known about the hydraulic signals and the corresponding signal transduction network and regulatory mechanisms. Here, using an epidermal-strip bioassay and laser-scanning confocal microscopy, we provide evidence that nitric oxide (NO) generation in Vicia faba guard cells can be induced by hydraulic signals. We used polyethylene glycol (PEG) 600 to simulate hypertonic conditions. This hydraulic signal led to stomatal closure and rapid promotion of NO production in guard cells. The effects were decreased by NO scavenger 2-(4-carboxyphenyl)-4,4,5, 5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO) and NO synthase (Enzyme Commission 1.14.13.39) inhibitor N(G)-nitro-L-Arg-methyl ester (L-NAME). These results indicate that PEG 6000 induces stomatal closure by promoting NO production. Cytochalasin B (CB) inhibited stomatal closure induced by PEG 6000 but did not prevent the increase of endogenous NO levels, indicating that microfilaments polymerization participate in stomatal closure induced by PEG 6000, and may act downstream of NO signaling. In addition, big vacuoles split into many small vacuoles were observed in response to PEG 6000 and sodium nitroprusside (SNP) treatment, and CB inhibited these changes of vacuoles, the stomatal closure was also been inhibited. Collectively, these results suggest that the stomatal closure induced by PEG 6000 may be intimately associated with NO levels, reorganization of actin filaments and the changes of vacuoles, showing a crude outline of guard-cells signaling process in response to hydraulic signals.
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http://dx.doi.org/10.1111/j.1399-3054.2009.01212.xDOI Listing
May 2009

[Clinical characteristics and therapy of severe Mycoplasma pneumonia in children].

Zhongguo Dang Dai Er Ke Za Zhi 2008 Dec;10(6):719-22

Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.

Objective: To study the clinical characteristics, therapeutic regimen and outcome of severe Mycoplasma pneumonia (MP) in children.

Methods: Clinical data of 79 children with MP, including 69 mild and 10 severe cases, were retrospectively analyzed. The 10 children with severe MP were followed-up.

Results: In severe MP cases, the fever duration prior to hospitalization and the total fever duration were more prolonged, peripheral blood leucocytes counts, C-reactive protein and erythrocyte sedimentation rate increased, and serum IgM and IgE levels increased as compared to mild MP cases. Of the 10 cases of severe MP, 4 manifested as pulmonary consolidation, 4 as pulmonary consolidation complicated by moderate to large pleural effusion and 2 as progressively worsening pulmonary radiographic findings. Nine severe MP cases were administered with glucocorticoid as well as antibiotics, and the therapeutic effect was satisfactory. In the convalescence stage, bronchofiberoscope lavages were used in 5 severe cases because of persistent pulmonary consolidation.

Conclusions: Severe MP was characterized by rapid progression, pulmonary consolidation, moderate to severe pleural effusion, obviously increased inflammatory indexes, and poor therapeutic reaction to simple macrolide antibiotics. Besides antibiotics, glucocorticoid should be used for severe MP cases as soon as possible. For severe cases with persistent pulmonary consolidation, bronchofiberoscope lavages are recommended.
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December 2008