Publications by authors named "Yali Wang"

386 Publications

Rapid differentiation between bacterial infections and cancer using a near-infrared fluorogenic probe.

Chem Sci 2020 Feb 26;11(12):3141-3145. Epub 2020 Feb 26.

State Key Laboratory of Bioactive Substances and Function of Natural Medicine, Beijing Key Laboratory of Active Substances Discovery and Drugability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College Beijing 100050 China

The reliable differentiation between bacterial infections and other pathologies is crucial for both diagnostics and therapeutic approaches. To accommodate such needs, we herein report the development of an activatable near-infrared fluorescent probe that could be applied in the ultrafast, ultrasensitive and specific detection of nitroreductase (NTR) activity in bacterial pathogens both and . Upon reaction with NTR, the nitro-group of the -nitro phenyl sulfonic moiety present in probe was reduced to an amino-group, resulting in a near-infrared fluorescence turn-on of the latent cyanine 7 fluorophore. Probe was capable of rapid and real-time quantitative detection of 0-150 ng mL NTR with a limit of detection as low as 0.67 ng mL. In addition, probe exhibited an outstanding performance of ultrafast measurements and suitable selectivity toward NTR to accurately sense intracellular basal NTR in ESKAPE bacterial pathogens. Most remarkably, probe was capable of noninvasively identifying bacterial infection sites without showing any significantly increased signal of tumour sites in the same animal within 30 min.
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http://dx.doi.org/10.1039/d0sc00508hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157330PMC
February 2020

A Pan-Cancer Analysis of the Oncogenic Role of Twinfilin Actin Binding Protein 1 in Human Tumors.

Front Oncol 2021 25;11:692136. Epub 2021 May 25.

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

Background: Understanding common and unique mechanisms driving oncogenic processes in human tumors is indispensable to develop efficient therapies. Recent studies have proposed Twinfilin Actin Binding Protein 1 (TWF1) as a putative driver gene in lung cancer, pancreatic cancer and breast cancer, however a systematic pan-cancer analysis has not been carried out.

Methods: Here, we set out to explore the role of TWF1 in 33 tumor types using TCGA (The Cancer Genome Atlas), GEO (Gene Expression Omnibus) dataset, Human Protein Atlas (HPA), and several bioinformatic tools.

Results: As part of our analysis, we have assessed expression across tumors. We found that over-expression of generally predicted poor OS for patients with tumors with high expression, such as mesothelioma, lung adenocarcinoma, cervical cancer and pancreatic adenocarcinoma. We also assessed the mutation burden of in cancer and the -associated survival of cancer patients, compared the phosphorylation of TWF1 between normal and primary tumor tissues and explored putative functional mechanisms in TWF1-mediated oncogenesis.

Conclusions: Our pan-cancer analysis provides a comprehensive overview of the oncogenic roles of TWF1 in multiple human cancers.
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http://dx.doi.org/10.3389/fonc.2021.692136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185641PMC
May 2021

Cruciasides C-G, monoterpenoid glycosides from Cruciata articulata.

Phytochemistry 2021 Jun 6;189:112821. Epub 2021 Jun 6.

School of Pharmaceutical Science and Technology, Health Sciences Platform, Tianjin University, Tianjin, 300072, China. Electronic address:

Cruciata articulata (L.) Ehrend. is a herbaceous species distributed in parts of Western Asia and the Mediterranean region. While research on other species in the Cruciata genus has revealed the presence of a range of flavonoids and terpenoids, few such studies have been conducted on C. articulata. Thus, in the current study, a phytochemical investigation of C. articulata was carried out. Molecular networking identified a large cluster of compounds sharing distinctive MS-MS fragmentation patterns that were targeted for isolation, leading to the isolation of five undescribed monoterpenoid glycosides, cruciasides C-G, along with two known monoterpenoid glycosides. The structures of these compounds were elucidated by using chemical and spectroscopic analyses, including 1D and 2D NMR, and MS-MS fragmentation. Structures for the ions observed in the MS-MS were proposed, and based on these fragmentation patterns, structures for several of the minor components observed in the molecular network were also proposed. All isolated compounds were tested for cytotoxic, anti-inflammatory, antimicrobial, and α-glucosidase inhibitory properties, but did not display any activity.
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http://dx.doi.org/10.1016/j.phytochem.2021.112821DOI Listing
June 2021

Trends of incidence and prognosis of primary adenocarcinoma of the bladder.

Ther Adv Urol 2021 Jan-Dec;13:17562872211018006. Epub 2021 May 24.

Department of Urology, Affiliated Lishui People's Hospital of Zhongda Hospital, Nanjing, China.

Background: Primary adenocarcinoma of the bladder (ACB) is a rare malignant tumor of the bladder with limited understanding of its incidence and prognosis.

Methods: Patients diagnosed with ACB between 2004 and 2015 were obtained from the SEER database. The incidence changes of ACB patients between 1975 and 2016 were detected by Joinpoint software. Nomograms were constructed based on the results of multivariate Cox regression analysis to predict overall survival (OS) and cancer-specific survival (CSS) in patients with ACB, and the constructed nomograms were validated.

Results: The incidence of ACB was trending down from 1991 to 2016. A total of 1039 patients were included in the study and randomly assigned to the training cohort (727) and validation cohort (312). In the training cohort, multivariate Cox regression showed that age, marital status, primary site, histology type, grade, AJCC stage, T stage, SEER stage, surgery, radiotherapy, and chemotherapy were independent prognostic factors for OS, whereas these were age, marital status, primary site, histology type, grade, AJCC stage, T/N stage, SEER stage, surgery, and radiotherapy for CSS. Based on the above Cox regression results, we constructed prognostic nomograms for OS and CSS in ACB patients. The C-index of the nomogram OS was 0.773 and the C-index of CSS was 0.785, which was significantly better than the C-index of the TNM staging prediction model. The area under the curve (AUC) and net benefit of the prediction model were higher than those of the TNM staging system. In addition, the calibration curves were very close to the ideal curve, suggesting appreciable reliability of the nomograms.

Conclusion: The incidence of ACB patients showed a decreasing trend in the past 25 years. We constructed a clinically useful prognostic nomogram for calculating OS and CSS of ACB patients, which can provide a personalized risk assessment for ACB patient survival.
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http://dx.doi.org/10.1177/17562872211018006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150450PMC
May 2021

Potential biomarkers for inherited thrombocytopenia 2 identified by plasma proteomics.

Platelets 2021 Jun 8:1-8. Epub 2021 Jun 8.

Laboratory of Radiation Biology, Department of Blood Transfusion, Laboratory Medicine Center, The Second Affiliated Hospital, Army Medical University, Chongqing, China.

Inherited thrombocytopenia 2 (THC2) is difficult to diagnose due to the lack of specific clinical characteristics and diagnostic methods. To identify potential plasma protein biomarkers for THC2, we collected the plasma samples from a THC2 family (9 THC2 and 15 non-THC2 members), enriched the medium and low abundant proteins using Proteominer and analyzed the protein profiles using the liquid chromatography-mass spectrometry in data independent acquisition mode. Initially, we detected 784 proteins in the plasma samples of this family and identified 27 up-regulated and 36 down-regulated in the THC2 group compared to the non-THC2 group (|log ratio| >1 and -value <0.05). To improve the predictive power, top eight dysregulated proteins (B7Z2B4, LTF, HP, ERN1, IGHV1-8, A0A0X9V9C4, VH6DJ, and D3JV41) were selected by an area under the curve-based random forest process to construct a clinical model. Multivariate analysis with random forest and support vector machine showed that the prediction model provided high discrimination ability for THC2 diagnosis (AUC: 1.000 and 0.967, respectively). The potential plasma protein biomarkers will be tested in more THC2 patients and other thrombocytopenia patients to further validate their specificity and sensitivity.
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http://dx.doi.org/10.1080/09537104.2021.1937594DOI Listing
June 2021

Liposomal honokiol promotes hair growth via activating Wnt3a/β-catenin signaling pathway and down regulating TGF-β1 in C57BL/6N mice.

Biomed Pharmacother 2021 Jun 5;141:111793. Epub 2021 Jun 5.

Department of Neuro-oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing 100071, China. Electronic address:

Liposomal honokiol isolated from the genus Magnolia has been found to have antiangiogenic, anti-inflammatory and antitumor properties. However, there has no report on its role in hair growth. Hair follicles are life-long cycled organelles that go through from anagen, catagen and telogen stages and are regulated by diverse signaling pathways, including Wnt/β-catenin, Notch, Epidermal growth factor (EGF) and Sonic hegehog (SHH). Wnt signals are essential for the initiation of hair follicle placode development and a new potential target of hair loss treatment. This study was designed to investigate the effect of liposomal honokiol (Lip-honokiol) on inducing hair anagen. We identified the hair grew out in advance in the shaving area of C57BL/6N mice after the treatment of liposomal honokiol (Lip-honokiol) by daily abdominal injection. We first demonstrated that Lip-Honokiol activated the Wnt3a/β-catenin pathway and downregulated the transforming growth factor-β1 (TGF-β1) to promote hair growth in mice via immunohistochemistry and immunofluorescence staining. These findings suggest that Lip-honokiol activated the Wnt/β-catenin pathway and accelerated the transfer from the telogen to anagen stage and finally promoted the hair growth.
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http://dx.doi.org/10.1016/j.biopha.2021.111793DOI Listing
June 2021

Circular RNAs in Hepatocellular Carcinoma: Emerging Functions to Clinical Significances.

Front Oncol 2021 14;11:667428. Epub 2021 May 14.

Department of Blood Transfusion, China-Japan Union Hospital of Jilin University, Changchun, China.

Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver and carries high morbidity and mortality. Diagnosing HCC at an early stage is challenging. Therefore, finding new, highly sensitive and specific diagnostic biomarkers for the diagnosis and prognosis of HCC patients is extremely important. Circular RNAs (circRNAs) are a class of non-coding RNAs with covalently closed loop structures. They are characterized by remarkable stability, long half-life, abundance and evolutionary conservation. Recent studies have shown that many circRNAs are expressed aberrantly in HCC tissues and have important regulatory roles during the development and progression of HCC. Hence, circRNAs are promising biomarkers for the diagnosis and prognosis of HCC. This review: (i) summarizes the biogenesis, categories, and functions of circRNAs; (ii) focuses on current progress of dysregulated expression of circRNAs in HCC with regard to regulation of the tumor hallmarks, "stemness" of cancer cells, and immunotherapy; (iii) highlights circRNAs as potential biomarkers and therapeutic targets for HCC; and (iv) discusses some of the challenges, questions and future perspectives of circRNAs research in HCC.
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http://dx.doi.org/10.3389/fonc.2021.667428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160296PMC
May 2021

Network-Based Online Survey Exploring Self-Reported Depression Among University and College Students During the Early Days of the COVID-19 Outbreak.

Front Psychiatry 2021 13;12:658388. Epub 2021 May 13.

Centre for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China.

The psychology of university and college students is immature, they are thus more likely to suffer from depression due to the COVID-19 pandemic. The present study aims to investigate the self-reported depression status of Chinese university and college students and explore its influencing factors. We conducted a network-based online survey, and a total of 17,876 participants completed the questionnaire. Depression was measured by the Self-Rating Depression Scale (SDS). Univariate analysis and multivariate logistic analysis were performed to explore the influencing factors of self-reported depression symptoms. The proportion of self-reported depression symptoms, mild self-reported depression symptoms, and moderate to severe (M/S) self-reported depression symptoms was 65.2, 53.7, and 11.5%, respectively. The mean score of self-reported depression was 54.8 ± 9.0. Female, personality type of partial introversion, junior college educational level, "moderate" or "high" self-perceived risk of infection, "moderately" or "highly" impacted by the outbreak, and being eager to go back to school were risk factors for M/S self-reported depression symptoms ( < 0.05). While, "moderate" or "high" concern about the outbreak, "moderate" or "high" satisfaction with pandemic prevention and control measures, and having health literacy on communicable diseases were protective factors for M/S self-reported depression symptoms ( < 0.05). The status of self-reported depression symptoms among university and college students was severer than expected, and the influencing factors were multifaceted. Government and school administrators should strengthen the dissemination of knowledge on disease prevention and control. Moreover, much attention should be paid to female and junior college students.
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http://dx.doi.org/10.3389/fpsyt.2021.658388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155487PMC
May 2021

Rational Design and Synthesis of Novel Dual PROTACs for Simultaneous Degradation of EGFR and PARP.

J Med Chem 2021 06 26;64(11):7839-7852. Epub 2021 May 26.

Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji-Rongcheng Center for Biomedicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Inspired by the success of dual-targeting drugs, especially bispecific antibodies, we propose to combine the concept of proteolysis targeting chimera (PROTAC) and dual targeting to design and synthesize dual PROTAC molecules with the function of degrading two completely different types of targets simultaneously. A library of novel dual-targeting PROTAC molecules has been rationally designed and prepared. A convergent synthetic strategy has been utilized to achieve high synthetic efficiency. These dual PROTAC structures are characterized using trifunctional natural amino acids as star-type core linkers to connect two independent inhibitors and E3 ligands together. In this study, gefitinib, olaparib, and CRBN or VHL E3 ligands were used as substrates to synthesize novel dual PROTACs. They successfully degraded both the epidermal growth factor receptor (EGFR) and poly(ADP-ribose) polymerase (PARP) simultaneously in cancer cells. Being the first successful example of dual PROTACs, this technique will greatly widen the range of application of the PROTAC method and open up a new field for drug discovery.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00649DOI Listing
June 2021

A palate of fluorescent corannulene derivatives: synthesis, spectroscopic properties, and bio-imaging application.

Chem Commun (Camb) 2021 Jun;57(47):5818-5821

School of Pharmaceutical Sciences and Technology, Health Sciences Platform, Tianjin University, 92 Weijin Road, Nankai, Tianjin 300072, China.

Reported here is a palate of fluorescent corannulene derivatives suitable for cellular imaging. They are derived from "tagging" corannulene with known fluorophores. The tagged corannulenes display strong fluorescence (φF > 0.25 in MeOH), good photostability and long emission wavelength (500 nm to 600 nm). Cell staining experiments indicate that several of them have excellent cell membrane permeability and targeting ability. In addition, we have found an unexpected, highly efficient energy transfer from corannulene to the pendant fluorophore. This has implications for many areas of corannulene research.
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http://dx.doi.org/10.1039/d1cc02307aDOI Listing
June 2021

Clinical and pathological analysis of renal biopsies of elderly patients in Northeast China: a single-center study.

Ren Fail 2021 Dec;43(1):851-859

The Department of Nephropathy, The Second Hospital of Jilin University, Changchun, China.

Purpose: To identify the clinical characteristics, histopathological features, and prognosis of kidney disease in a large cohort of elderly patients from Northeast China.

Methods: We retrospectively analyzed the renal disease spectrum in 7,122 patients who underwent renal biopsies at the Second Hospital of Jilin University from 2006 to 2020. Patients were grouped according to age: below 60 years (non-elderly group,  = 5923) and at least 60 years (elderly group,  = 1199). The clinical and pathological characteristics of renal biopsy patients in the groups were analyzed using the -test and chi-square test.

Results: Compared with the non-elderly group, the elderly group had significantly fewer patients with primary glomerulonephritis, but more patients with tubulointerstitial disorders ( < .05). The incidence of IgA nephropathy, mesangial proliferative glomerulonephritis, and lupus nephritis was significantly lower in elderly patients than in non-elderly patients. The incidence of membranous nephropathy, membranoproliferative glomerulonephritis, diabetic nephropathy, hypertensive nephropathy, systemic vasculitis-associated renal damage, and amyloid nephropathy was significantly higher in elderly patients than in non-elderly patients ( < .05). The incidence of perinephric hematoma (≥4 cm) in elderly patients with renal biopsy was lower than that in non-elderly patients. We noted that 79.9% of primary glomerulonephritis patients who received immunosuppressive therapy showed a remission rate of 83.5%.

Conclusion: The spectrum of kidney disease in the elderly is different from that in the younger population.
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http://dx.doi.org/10.1080/0886022X.2021.1923527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118502PMC
December 2021

Relationship between hyperuricemia and serositis in patients with lupus nephritis.

Int Urol Nephrol 2021 May 10. Epub 2021 May 10.

The Department of Nephropathy, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun, 130041, Jilin Province, China.

Purpose: To investigate the clinical and pathological characteristics of lupus nephritis (LN) patients with serositis and analyse the relationship between serositis and hyperuricemia (HUA) in LN patients in northeast China.

Methods: The data of patients with LN diagnosed by renal biopsy in our hospital from April 2013 to May 2020 were retrospectively analyzed. The differences between the non-serositis and serositis groups were compared by t tests and Chi-square test. Factors with P < 0.05 in the univariate analyses were investigated further using binary logistic regression analysis to investigate the independent risk factors of serositis in patients with LN.

Results: LN patients with serositis were more likely to have fever, hypertension, neuropsychiatric and hematological involvement than those without serositis (P < 0.05). Compared with the non-serositis group, LN patients with serositis were prone to have HUA, high D-dimer, high triglycerides, and had significant differences in the levels of plasma albumin (Alb), estimated glomerular filtration rate (eGFR), erythrocyte sedimentation rate, C-reactive protein, complement C3, 24-h urinary protein, pathological types, pathological score and SLEDAI score. Logistic regression analysis showed that HUA was one of risk factors for serositis in LN patients. The rate of complete remission in LN patients with serositis was significantly lower (P < 0.05) and the rate of no remission and mortality were significantly higher (P < 0.05) than LN patients without serositis.

Conclusion: LN patients with serositis had more severe clinical and pathological manifestations, higher systemic lupus erythematosus (SLE) activity and worse prognosis. Hyperuricemia is associated with serositis in LN patients.
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http://dx.doi.org/10.1007/s11255-021-02873-zDOI Listing
May 2021

Immunogenicity and safety of 7-valent pneumococcal conjugate vaccine (PCV7) in children aged 2-5 years in China.

Vaccine 2021 Jun 6;39(25):3428-3434. Epub 2021 May 6.

Experimental Center for Basic Medical Teaching, Capital Medical University, Beijing, China. Electronic address:

Background: The widespread use of pneumococcal conjugate vaccines (PCVs) has significantly decreased pneumococcal disease worldwide. However, China has not adopted PCVs in their national immunization schedules and had only approved these vaccines for children aged 2-15 months by 2020.

Methods: In an open-label trial, enrolled healthy children aged 2-5 years old were randomized 1:1 and divided into a 7-valent pneumococcal conjugate vaccine (PCV7) group and a Haemophilus influenzae type b conjugate vaccine (Hib) group. Children in the PCV7 group received a single dose of PCV7, and the Hib group received a single dose of Hib vaccine. Blood samples were collected before and 6 months after vaccination. Immunogenicity and safety of PCV7 were assessed at prespecified time points.

Results: Six months after a single dose of PCV7, children in the PCV7 group for all 7 serotypes, IgG mean concentrations (GMCs) and opsonophagocytic geometric mean titres (GMTs) were significantly higher (P < .001) than at baseline, and the proportion of IgG ≥ 0.35 µg/mL ranged from 90.0% to 100%. Although the antibody level increased with age, preexisting antibodies did not induce hyporesponsiveness to PCV7. In the Hib group, the antibody levels were not significantly different or had changed slightly at 6 months. PCV7 was well tolerated in all age groups, and no serious adverse events (AEs) emerged during this study.

Conclusions: A single dose of PCV7 was immunogenic and safe for Chinese children aged 2-5 years, and the preexisting antibodies against the PCV7 serotypes did not change the response to vaccination. The findingssupported the effectiveness of PCV7 in this age group. PCVs with broader serotype coverage are expected to expand pneumococcal disease protection.
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http://dx.doi.org/10.1016/j.vaccine.2021.04.037DOI Listing
June 2021

Diterpenoids from the seeds of Euphorbia lathyris and their anti-inflammatory activity.

Bioorg Chem 2021 Jul 26;112:104944. Epub 2021 Apr 26.

Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address:

Twelve previously undescribed diterpenoids, euplarisans A-L (1-12), including one premyrsinane and eleven lathyranes, along with ten known analogues 13-22 were isolated from the seeds of Euphorbia lathyris. Their chemical structures were delineated by spectroscopic analysis and single-crystal X-ray diffraction. Interestingly, both 5 and 6 possessed an unusual trans-gem-dimethylcyclopropane as structural features and compound 8 was elucidated as premyrsinane-type diterpenoid. Meanwhile, a plausible biogenetic pathway for compounds 1-12 was proposed. In the anti-inflammatory bioassay, compounds 1, 2, 4, 13, 16, and 18 markedly inhibited the nitric oxide production in LPS-induced RAW264.7 macrophage cells. Compound 1 showed a more remarkable anti-inflammatory effect than others. It inhibited the generation of inflammatory cytokines (IL-1β, IL-6, and TNF-α) and also obviously decreased the expression of iNOS, COX-2, and p-IκBα in a dose-dependent manner. The structure-activity relationships (SARs) of these diterpenoids were also discussed.
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http://dx.doi.org/10.1016/j.bioorg.2021.104944DOI Listing
July 2021

Clinical effects of breast milk enema on meconium evacuation in premature infants: study protocol for a randomized controlled trial.

Trials 2021 Apr 26;22(1):304. Epub 2021 Apr 26.

Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China.

Background: Delayed meconium evacuation is an important cause of intestinal dysfunction in preterm infants. There are many methods to induce defecation in preterm infants: however, the effects are controversial. Finding a new intervention method to promote meconium evacuation in premature infants is necessary. Therefore, in the proposed study, the effectiveness of breast milk enema on complete meconium evacuation and time to achieve full enteral feeding will be investigated in preterm infants.

Methods/design: The study is a randomized, open-label, parallel-group, and single-center clinical trial. A total of 294 preterm infants will be recruited and stratified based on gestational age. Then, the infants will be assigned in a randomized block design to the intervention and control groups with a 1:1 ratio. Preterm infants in the control and intervention groups will receive saline enema and breast milk enema, respectively. The primary outcomes will be the time to achieve complete meconium evacuation from birth and time to achieve full enteral feeding from birth in preterm infants. The secondary outcomes will include hospitalization days, body weight at discharge, duration of total parenteral nutrition, cholestasis, and adverse events.

Discussion: The results of this trial will determine whether breast milk enema shortens the time to complete meconium evacuation and the time to achieve full enteral feeding in extremely preterm and preterm infants. Furthermore, the study results may provide a new, safe, inexpensive, and easy-to-use intervention to effectively evacuate meconium in preterm infants.

Trial Registration: ISRCTN Registry ISRCTN17847514 . Registered on September 14, 2019.
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http://dx.doi.org/10.1186/s13063-021-05261-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074446PMC
April 2021

Epidemiological and Clinical Characteristics of 217 Cases of COVID-19 in Jiangsu Province, China.

Med Sci Monit 2021 Apr 12;27:e930853. Epub 2021 Apr 12.

Department of Respiratory Medicine, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China (mainland).

BACKGROUND COVID-19 has become a worldwide epidemic disease and is a public health crisis. We aim to provide evidence for clinical diagnosis and assessment of severity by analyzing patients' clinical data and early laboratory results and exploring the correlation between laboratory results and clinical classification. MATERIAL AND METHODS We enrolled 283 cases of suspected and diagnosed COVID-19 from 16 hospitals in Jiangsu Province from January to April 2020. The routine laboratory blood examinations, T lymphocyte subsets, and biochemical and coagulation function among different populations were contrasted by t test and chi-square (χ²) test. RESULTS Cough, fever, and dyspnea could be helpful to diagnose COVID-19 infection (P<0.05). Patients who were older or had comorbidities tended to become severe and critical cases. Among all the patients, the most obvious abnormal laboratory results were higher neutrophil count, CRP, total bilirubin, BUN, CRE, APTT, PT, and D-dimer, and lower blood platelet and lymphocyte count. CD3⁺ T cell, CD4⁺ T cell, and CD8⁺ T cell counts gradually decreased with exacerbation of the disease (P<0.05). CONCLUSIONS Cough and fever were the most common symptom. Patients with comorbidities were in more serious condition. The detection of inflammatory indexes, coagulation function, lymphocyte subsets, and renal function can help diagnose and assess the severity of COVID-19.
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http://dx.doi.org/10.12659/MSM.930853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051165PMC
April 2021

The complete mitochondrial genome of a cave-dwelling loach (Teleostei: Nemacheilidae).

Mitochondrial DNA B Resour 2021 Mar 26;6(3):1209-1211. Epub 2021 Mar 26.

School of Karst Sciences, Guizhou Normal University, Guiyang, Guizhou, PR China.

belong to the genus (Teleostei, Nemacheilidae), endemic to Guizhou Province, Southwestern China. In this study, the complete mitochondrial genome of was sequenced and reported for the first time. The circular mitogenome was 16,576 bp in length and consisted of 13 protein-coding genes, 2 ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and 1 non-coding control region. The overall base composition was 30.79% A, 27.62% T, 25.46% C, and 16.13% G with 41.59% GC content. Phylogenetic analysis using mitochondrial genomes of 40 species showed that all species clustered as one monophyletic clade, and was the closest to ( + ()).
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http://dx.doi.org/10.1080/23802359.2021.1899861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008877PMC
March 2021

Online-Based Survey on College Students' Anxiety During COVID-19 Outbreak.

Psychol Res Behav Manag 2021 29;14:385-392. Epub 2021 Mar 29.

Henan Provincial Center for Disease Control and Prevention, Zhengzhou, Henan, People's Republic of China.

Purpose: Studies have suggested that public health emergencies can have many psychological effects on college students, therefore, the aim of this study is to investigate current situation of college students' anxiety and its determinants in the time of an unexpected pandemic.

Patients And Methods: We conducted convenience sampling to collect the data through network-based online questionnaires in February 2020, a total of 17,876 college students were included in the analysis. Chi-square test and multivariate logistic were used to identify the associations between the outbreak experiences and anxiety detection.

Results: This study found that detection rate of anxiety among college students was 18.2%. The differences in male students, students whose self-perceived risk of infection were high, who were greatly affected by the outbreak, eager to go back to school, reluctant to leave home and stay at home enough were of statistical significance among different anxiety level (OR>1, P<0.05). And the severe anxiety rate of students who living in cities was significantly higher (2.337[1.468, 3.721]).

Conclusion: Although our results show that anxiety among college students was at a low level, various universities should focus on the online activities and develop appropriate epidemic management plans to prevent their feelings of worry, tension and panic.
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http://dx.doi.org/10.2147/PRBM.S298539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018558PMC
March 2021

Beta-endorphin inhibits the inflammatory response of bovine endometrial cells through δ opioid receptor in vitro.

Dev Comp Immunol 2021 Aug 26;121:104074. Epub 2021 Mar 26.

College of Veterinary Medicine, Yangzhou University, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou, 225009, China; Joint International Research Laboratory of Agriculture and Agriproduct Safety of the Ministry of Education, Yangzhou, Jiangsu, 225009, China. Electronic address:

Postpartum uterine infections are common reproductive diseases in postpartum cows. Evidence has shown that plasma β-endorphins increase during bovine uterine inflammation. However, the effect of β-endorphins on the inflammatory response in bovine endometrium has not been clarified. The aim of this study was to investigate the effect of β-endorphins on the inflammatory response of bovine endometrial epithelial and stromal cells, and to explore the possible mechanism. The cells were treated with E. coli lipopolysaccharide (LPS) to simulate inflammation, which was characterized by the significant activation of NF-κB signaling pathway and the increased gene expression of the downstream proinflammatory cytokines (approximately 1.2- to 15-fold increase, P < 0.05). By using Western blot and qPCR techniques, we found that β-endorphins inhibited the key protein expression of NF-κB pathway, and the gene expressions of TNF, IL1B, IL6, CXCL8, nitric oxide synthase 2, and prostaglandin-endoperoxide synthase 2 (P < 0.05). The co-treatment of β-endorphins and opioid antagonists showed that the anti-inflammatory effect of β-endorphins could be blocked (P < 0.05) by non-selective opioid antagonist naloxone or δ opioid receptor antagonist ICI 154129, but not the μ opioid receptor antagonist CTAP (P > 0.05). In conclusion, β-endorphins may inhibit the inflammatory response of bovine endometrial epithelial and stromal cells through δ opioid receptor.
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http://dx.doi.org/10.1016/j.dci.2021.104074DOI Listing
August 2021

Long noncoding RNA VESTAR regulates lymphangiogenesis and lymph node metastasis of esophageal squamous cell carcinoma by enhancing VEGF-C mRNA stability.

Cancer Res 2021 Mar 26. Epub 2021 Mar 26.

Laboratory of Molecular Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.

Lymph node (LN) metastasis is one of the most malignant clinical features in patients with esophageal squamous cell carcinoma (ESCC). Understanding the mechanism of LN metastasis will provide treatment strategies for ESCC patients. Long noncoding RNAs (lncRNA) play a critical role in the development and progression of human cancers. However, the role and mechanism of lncRNAs in LN metastasis remain largely unknown. Here we show that VEGF-C mRNA stability-associated long noncoding RNA (VESTAR) is involved in LN metastasis of ESCC. VESTAR was overexpressed in ESCC tissues and was predictive of poor prognosis in patients with ESCC. In ESCC, NXF1 and SRSF3 facilitated nuclear export of VESTAR to the cytoplasm, which was associated with LN metastasis. Depletion of VESTAR inhibited ESCC-associated lymphangiogenesis and lymphatic metastasis. Mechanistically, VESTAR directly bound and stabilized VEGF-C mRNA. VESTAR also interacted with HuR, a positive regulator of VEGF-C mRNA stability, and increased HuR binding to VEGF-C mRNA. Our study reveals a novel lncRNA-guided mechanism of LN metastasis in ESCC and may provide a potential target for treatment of ESCC lymphatic metastasis.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-1713DOI Listing
March 2021

A lysosome-targeted probe for the real-time detection of hypobromous acid in living human cancer cells.

Analyst 2021 Apr;146(8):2484-2489

School of Pharmaceutical Sciences and Technology, Health Sciences Platform, Tianjin University, 92 Weijin Road, Nankai District, Tianjin 300072, China.

We reported here a naphthalimide-based fluorescent probe LysOBr that localizes in the lysosome in live cells. LysOBr exhibits excellent HOBr selectivity and desirable optical properties. It can quantitatively detect lysosomal HOBr at 0-20 μM, with a detection limit of 243 nM. The short (4 s) response time allows real-time HOBr detection and imaging, as shown with studies in live HeLa cancer cells. It is thus the most rapidly responsive HOBr probe to date, among the most selective ones, and the first probe that is lysosome-specific with a "turn-on" signal. The probe structure is modular, and convenient structural modification should lead to other organelle-specific probes.
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http://dx.doi.org/10.1039/d1an00147gDOI Listing
April 2021

Alkaloids of Delphinium grandiflorum and their implication to HO-induced cardiomyocytes injury.

Bioorg Med Chem 2021 May 17;37:116113. Epub 2021 Mar 17.

Wuya College of Innovation, School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address:

Three new diterpenoid alkaloids (1-3), and eight known alkaloids (4-11) were isolated from the aerial parts of Delphinium grandiflorum. Grandifline A (1) represents an unprecedented diterpenoid alkaloid ring system featuring a C-7NC17 hemiaminal moiety and a lactone fragment through the linkage of C-17OC19 unit. And we named this newly-discovered class of rearranged C-diterpenoid alkaloid scaffold as grandiflodines (B-12). Grandifline B (2) is the first naturally-occurring 7,17-secolycoctonine diterpenoid alkaloid with a C-7OC17 unit forming a hemiacetal. Their structures were elucidated via spectroscopic data and single-crystal X-ray diffraction analysis. The protective effects of compounds 1-11 on HO-induced cardiomyocytes injury were assayed. And compounds 6 and 10 showed significant protective effects, with IC values of 1.881 ± 0.680 μM and 1.904 ± 0.750 μM, respectively. Further, compound 6 could reduce oxidative damage by inhibiting cell death via the AMPK/AKT/mTOR signaling pathway in HO-induced H9C2 cells.
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http://dx.doi.org/10.1016/j.bmc.2021.116113DOI Listing
May 2021

Trajectories of body mass index and risk of incident hypertension among a normal body mass index population: A prospective cohort study.

J Clin Hypertens (Greenwich) 2021 Jun 20;23(6):1212-1220. Epub 2021 Mar 20.

Department of Cardiology, Department of Library and Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China.

It is unclear whether there are different body mass index (BMI) trajectories among a population with normal BMI levels, and the association between BMI patterns and incident hypertension is not well characterized. This prospective cohort study includes surveys conducted at baseline and three follow-ups. 3939 participants who are free of hypertension at baseline or first two follow-ups were enrolled. At baseline, the age of participants ranged from 35 to 82 years and the mean age was 45.9 years. The BMI trajectories were identified using latent mixture modeling with data from the baseline and first two follow-ups. The effects of different BMI trajectories on the development of hypertension were analyzed using a Cox proportional hazard model. Four distinct BMI trajectories were identified over the study period (2004-2010): normal-stable (n = 1456), normal-increasing (n = 2159), normal-fluctuated (n = 166), and normal-sharp-increasing (n = 158). Relative to the normal-stable BMI group, the hazard ratios (HRs) and 95% confidence intervals (CIs) after adjustment for confounding factors of the normal-increasing, normal-fluctuated, and normal-sharp-increasing groups were 1.244 (1.103-1.402), 1.331 (1.008-1.756), and 1.641 (1.257-2.142), respectively. Additionally, subgroup analysis showed that the normal-fluctuated BMI trajectory was associated with a significantly higher risk of hypertension only in women (HR = 1.362; 95% CI = 1.151-1.611). The BMI trajectories were significant predictors of hypertension incidence, and increasing BMI trajectories within the currently designated normal range were associated with an increased hypertension risk, especially in women.
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http://dx.doi.org/10.1111/jch.14241DOI Listing
June 2021

Neuropsychiatric Adverse Events During 12 Months of Treatment With Efavirenz in Treatment-Naïve HIV-Infected Patients in China: A Prospective Cohort Study.

Front Psychiatry 2021 24;12:579448. Epub 2021 Feb 24.

Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China.

Efavirenz (EFV) is widely used in antiretroviral therapy (ART), but the incidence and risk factors of neuropsychiatric adverse events (NPAEs) after EFV treatment have rarely been studied in Chinese ART naïve patients. This prospective cohort study assessed HIV-infected patients initiating antiretroviral treatment with EFV to determine prevalence of and factors associated with NPAEs over a 12-month follow-up period using the Hospital Anxiety and Depression Scale (HADS) and the Pittsburgh Sleep Quality Index (PSQI). A total of 546 patients were enrolled. Prevalence of anxiety, depression, and sleep disturbances at baseline were 30.4, 22.7, and 68.1%, respectively. Six patients discontinued treatment due to drug related NPAEs. Treatment was associated with improvements in HADS-A, HADS-D, and PSQI scores over the 12-month follow-up, and the frequencies of patients with anxiety, depression, and sleep disturbances significantly decreased after 12 months. Abnormal baseline HADS-A, HADS-D, and PSQI scores and other factors, including high school education or lower income, unemployment, divorce, and WHO III/IV stages, were associated with severe neuropsychiatric disorders over the 12 months. These findings suggested EFV discontinuation due to NAPEs was low, and the HADS-A, HADS-D, and PSQI scores after 12 months of EFV treatment were associated with several risk factors. The clinicians should keep in mind and routinely screen for the risk factors associated with neuropsychiatric disorders in HIV-infected patients.
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http://dx.doi.org/10.3389/fpsyt.2021.579448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943719PMC
February 2021

Divergent evolution profiles of DD37D and DD39D families of Tc1/mariner transposons in eukaryotes.

Mol Phylogenet Evol 2021 Aug 10;161:107143. Epub 2021 Mar 10.

College of Animal Science & Technology, Yangzhou University, Yangzhou, Jiangsu 225009, China. Electronic address:

DNA transposons play a significant role in shaping the size and structure of eukaryotic genomes. The Tc1/mariner transposons are the most diverse and widely distributed superfamily of DNA transposons and the structure and distribution of several Tc1/mariner families, such as DD35E/TR, DD36E/IC, DD37E/TRT, and DD41D/VS, have been well studied. Nonetheless, a greater understanding of the structure and diversity of Tc1/mariner transposons will provide insight into the evolutionary history of eukaryotic genomes. Here, we conducted further analysis of DD37D/maT and DD39D (named Guest, GT), which were identified by the specific catalytic domains DD37D and DD39D. Most transposons of the maT family have a total length of approximately 1.3 kb and harbor a single open reading frame encoding a ~ 346 amino acid (range 302-398 aa) transposase protein, flanked by short terminal inverted repeats (TIRs) (13-48 base pairs, bp). In contrast, GTs transposons were longer (2.0-5.8 kb), encoded a transposase protein of ~400 aa (range 140-592 aa), and were flanked by short TIRs (19-41 bp). Several conserved motifs, including two helix-turn-helix (HTH) motifs, a GRPR (GRKR) motif, a nuclear localization sequence, and a DDD domain, were also identified in maT and GT transposases. Phylogenetic analyses of the DDD domain showed that the maT and GT families each belong to a monophyletic clade and appear to be closely related to DD41D/VS and DD34D/mariner. In addition, maTs are mainly distributed in invertebrates (144 species), whereas GTs are mainly distributed in land plants through a small number of GTs are present in Chromista and animals. Sequence identity and phylogenetic analysis revealed that horizontal transfer (HT) events of maT and GT might occur between kingdoms and phyla of eukaryotes; however, pairwise distance comparisons between host genes and transposons indicated that HT events involving maTs might be less frequent between invertebrate species and HT events involving GTs may be less frequent between land plant species. Overall, the DD37D/maT and DD39D/GT families display significantly different distribution and tend to be identified in more ancient evolutionary families. The discovery of intact transposases, perfect TIRs, and target site duplications (TSD) of maTs and GTs illustrates that the DD37D/maT and DD39D/GT families may be active. Together, these findings improve our understanding of the diversity of Tc1/mariner transposons and their impact on eukaryotic genome evolution.
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http://dx.doi.org/10.1016/j.ympev.2021.107143DOI Listing
August 2021

Antituberculosis Drugs (Rifampicin and Isoniazid) Induce Liver Injury by Regulating NLRP3 Inflammasomes.

Mediators Inflamm 2021 19;2021:8086253. Epub 2021 Feb 19.

Nanchong Key Laboratory of Individualized Drug Therapy, Nanchong, Sichuan, China.

Patients being treated for pulmonary tuberculosis often suffer liver injury due to the effects of anti-TB drugs, and the underlying mechanisms for those injuries need to be clarified. In this study, rats and hepatic cells were administrated isoniazid (INH) and rifampin (RIF) and then treated with NLRP3-inflammasome inhibitors (INF39 and CP-456773) or NLRP3 siRNA. Histopathological changes that occurred in liver tissue were examined by H&E staining. Additionally, the levels IL-33, IL-18, IL-1, NLRP3, ASC, and cleaved-caspase 1 expression in the liver tissues were also determined. NAT2 and CYP2E1 expression were identified by QRT-PCR analysis. Finally, assays were performed to examine the effects of siRNA targeting NLRP3. Treatment with the antituberculosis drugs caused significant liver injuries, induced inflammatory responses and oxidative stress (OS), activated NLRP3 inflammasomes, reduced the activity of drug-metabolizing enzymes, and altered the antioxidant defense system in rats and hepatic cells. The NLRP3 inflammasome was required for INH- and RIF-induced liver injuries that were produced by inflammatory responses, OS, the antioxidant defense system, and drug-metabolizing enzymes. This study indicated that the NLRP3 inflammasome is involved in antituberculosis drug-induced liver injuries (ATLIs) and suggests NLRP3 as a potential target for attenuating the inflammation response in ATLIs.
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http://dx.doi.org/10.1155/2021/8086253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914095PMC
February 2021

Caspase-Independent Regulated Necrosis Pathways as Potential Targets in Cancer Management.

Front Oncol 2020 16;10:616952. Epub 2021 Feb 16.

Department of General Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Regulated necrosis is an emerging type of cell death independent of caspase. Recently, with increasing findings of regulated necrosis in the field of biochemistry and genetics, the underlying molecular mechanisms and signaling pathways of regulated necrosis are gradually understood. Nowadays, there are several modes of regulated necrosis that are tightly related to cancer initiation and development, including necroptosis, ferroptosis, parthanatos, pyroptosis, and so on. What's more, accumulating evidence shows that various compounds can exhibit the anti-cancer effect inducing regulated necrosis in cancer cells, which indicates that caspase-independent regulated necrosis pathways are potential targets in cancer management. In this review, we expand the molecular mechanisms as well as signaling pathways of multiple modes of regulated necrosis. We also elaborate on the roles they play in tumorigenesis and discuss how each of the regulated necrosis pathways could be therapeutically targeted.
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http://dx.doi.org/10.3389/fonc.2020.616952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921719PMC
February 2021

Local Staging of Colon Cancer: A Cross-Sectional Analysis for Diagnostic Performance of Magnetic Resonance Imaging and by Experience.

Cancer Invest 2021 May 16;39(5):379-389. Epub 2021 Mar 16.

Nuclear Medicine, The Third Hospital of Hebei Medical University, Shijiazhuang, China.

Preoperative magnetic resonance imaging was analyzed by four radiologists regarding local tumor staging (T and N) and the presence of extramural vascular involvement. An astonishingly high sensitivity for the detection of T 3/4 tumors ( (quadratic weighted statistics constant) = 0.67), with considerably lower sensitivity for T 3 cd/4 tumors ( = 0.51), high sensitivity for serosal involvement 76-87% ( = 0.65) and extramural vascular involvement (87-98%,  = 0.56). Sensitivity and specificity for lymph node involvement is lower ( = 0.57). Magnetic resonance imaging with adequate experience can accurately detect tumors with invasion through the bowel wall and their prognostic factors.
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http://dx.doi.org/10.1080/07357907.2021.1897610DOI Listing
May 2021

A native, highly active Tc1/mariner transposon from zebrafish (ZB) offers an efficient genetic manipulation tool for vertebrates.

Nucleic Acids Res 2021 02;49(4):2126-2140

College of Animal Science & Technology, Yangzhou University, Yangzhou, Jiangsu 225009, China.

New genetic tools and strategies are currently under development to facilitate functional genomics analyses. Here, we describe an active member of the Tc1/mariner transposon superfamily, named ZB, which invaded the zebrafish genome very recently. ZB exhibits high activity in vertebrate cells, in the range of those of the widely used transposons piggyBac (PB), Sleeping Beauty (SB) and Tol2. ZB has a similar structural organization and target site sequence preference to SB, but a different integration profile with respect to genome-wide preference among mammalian functional annotation features. Namely, ZB displays a preference for integration into transcriptional regulatory regions of genes. Accordingly, we demonstrate the utility of ZB for enhancer trapping in zebrafish embryos and in the mouse germline. These results indicate that ZB may be a powerful tool for genetic manipulation in vertebrate model species.
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http://dx.doi.org/10.1093/nar/gkab045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913693PMC
February 2021

Novel Oxovanadium Complex VO(hntdtsc)(NPIP): Anticancer Activity and Mechanism of Action on HeLa Cells.

Front Pharmacol 2020 8;11:608218. Epub 2021 Feb 8.

School of Pharmacy, Lanzhou University, Lanzhou, China.

Oxovanadium complexes, particularly vanadyl (IV) derivatives with hybrid ligands of Schiff base and polypyridyl, have been demonstrated to possess great anticancerous therapeutic efficacy. However, most of the studies on the activity of these oxovanadium complexes have mainly focused on studies, and animal studies are extremely scarce. Based on the antitumor test results of four novel oxovanadium complexes in our previous work, this work further conducted a comprehensive antitumor activity study and on VO(hntdtsc)(NPIP), which owned the strongest inhibitory activity on multiple tumor cell proliferation. The cellular mechanism study suggested that VO(hntdtsc)(NPIP) inhibited the cell proliferation arresting the cell cycle at G0/G1 phase through the p16-cyclin D1-CDK4-p-Rb pathway and inducing cell apoptosis through mitochondrial-dependent apoptosis pathway on HeLa cells. Inconsistent with the effects , VO(hntdtsc)(NPIP) significantly inhibited the growth of tumor and induced the apoptosis of cancer cells in mice xenograft models according to the results of nude mice image detection, H&E pathological examination, and immunohistochemical detection of p16/Ki-67 protein expression. Collectively, all the results, particularly studies demonstrated that VO(hntdtsc)(NPIP) hold a potential to be the lead compound and further to be an anticervical cancer drug.
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http://dx.doi.org/10.3389/fphar.2020.608218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897675PMC
February 2021