Publications by authors named "Zhichao Wang"

144 Publications

Citrus Alkaline Extracts Inhibit Senescence of A549 Cells to Alleviate Pulmonary Fibrosis via the β-Catenin/P53 Pathway.

Med Sci Monit 2021 Mar 12;27:e928547. Epub 2021 Mar 12.

Department of Respiratory Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China (mainland).

BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a disease related to aging, which has become increasingly prevalent as the population has aged. However, there remains no effective treatment for the disease. Alveolar epithelial type II cell (AEC II) senescence plays an important role in the occurrence and development of IPF. Therefore, enhancing our understanding of aging AEC IIs might facilitate the development of a new therapeutic strategy for the prevention and treatment of IPF. The aim of this study was to investigate the effect of citrus alkaline extracts (CAE) on senescence in A549 cells and elucidate the mechanism by which CAE function. MATERIAL AND METHODS Adriamycin RD (ARD) induces the senescence of A549 cells. Relevant indicators were identified following administration of 3 concentrations of CAE (50 μg/mL, 100 μg/mL, and 200 μg/mL) to A549 cells. RESULTS CAE inhibited senescence in ARD-induced A549 cells. It inhibited p16, p21, p53, and a senescence-associated secretory phenotype, and reduced expression of the senescence-related positive cells of ß-galactosidase. Further study revealed that activation of the ß-catenin signaling pathway is closely associated with p53. CAE inhibited senescence in A549 cells via the ß-catenin/p53 pathway. Further, inhibition of b-catenin was associated with reduced expression levels of p53 and p21, and the anti-aging effects of CAE were enhanced. When expression of p53 was inhibited, expression levels of ß-catenin also tended to decrease. CONCLUSIONS In summary, our study showed that CAE can inhibit aging in A549 cells to alleviate pulmonary fibrosis, and thus limit the secretion of the extracellular matrix and collagen in lung fibroblasts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12659/MSM.928547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962417PMC
March 2021

Culture-negative versus culture-positive in pyogenic spondylitis and analysis of risk factors for relapse.

Br J Neurosurg 2021 Mar 8:1-5. Epub 2021 Mar 8.

Spine Surgery, Affiliated Hospital of Qingdao University, Qingdao, China.

Objectives: This study aims to compare and analyze the clinical features, diagnosis, treatment and prognosis of culture-negative and culture-positive primary pyogenic spondylitis.

Methods: In a retrospective analysis, 202 cases of adult primary pyogenic spondylitis with complete clinical data in our hospital from January 2013 to January 2020 were divided into two groups according to bacterial culture results: culture negative ( = 126) and culture positive ( = 76). We compare the clinical characteristics, diagnosis, treatment and prognosis of patients with different culture results.

Results: The culture positive rate was 37.62% (76/202). There were no significant differences in age, gender, affected segment, spinal abscess, diabetes mellitus, course of disease, surgery, recurrence, and follow-up time between the two groups (>.05). There were statistically significant differences in hospital admission erythrocyte sedimentation rate (ESR), admission C-reactive protein (CRP), admission white blood cell (WBC) count, discharge ESR, discharge CRP, ESR decline rate, CRP (<.05). There were statistically significant differences in the rate of decline, hospitalization days, and body temperature ≥38 °C (<.05). Higher CRP levels on admission, antibiotic treatment time <6 weeks, and body temperature ≥ 38 °C are independent risk factors for infection recurrence.

Conclusions: The culture-negative group's admission WBC, admission ESR, admission CRP, discharge ESR, discharge CRP, ESR decline rate, CRP decline rate, and hospital stay were lower than the culture positive group, the difference was statistically significant (<.05). The independent risk factors for infection recurrence are higher CRP levels in hospital admission, antibiotic treatment time <6 weeks, and body temperature ≥ 38 °C.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/02688697.2021.1896677DOI Listing
March 2021

Distribution Patterns (7B Rule) and Characteristics of Large Congenital Melanocytic Nevi: A Retrospective Cohort Study in China.

Front Med (Lausanne) 2021 19;8:637857. Epub 2021 Feb 19.

Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Large congenital melanocytic nevus has a high risk of malignancy. However, few studies have summarized its characteristics, treatments, outcomes and malignancy incidence in Chinese patients. This paper reviews a retrospective cohort study evaluating 1,171 patients from Shanghai Ninth People's Hospital between 1 January 1989 and 31 August 2019 using electronic medical records and phone calls to collect clinical and pathological data in which 133 patients were diagnosed with a large congenital melanocytic nevus. Three patients relapsed, and none developed melanoma among the qualified patients. Besides, a new "7B" rule for distribution patterns of large congenital melanocytic nevi was proposed, including bonce, bolero, back, bathing trunk, breast/belly, body extremity, and body. The most common distribution pattern of large congenital melanocytic nevi was bonce, and all blue nevi distributed as bonce. Statistical analysis showed a significant difference ( = 0.0249) in the "7B" patterns between the melanocytic nevus and the neuronevus. In conclusion, the malignancy rate of large congenital melanocytic nevi is much lower in China than in other regions and people of other races. The pathology of large congenital melanocytic nevus may decide its "7B" distribution pattern.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmed.2021.637857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933508PMC
February 2021

GPR4 signaling is essential for the promotion of acid-mediated angiogenic capacity of endothelial progenitor cells by activating STAT3/VEGFA pathway in patients with coronary artery disease.

Stem Cell Res Ther 2021 Feb 25;12(1):149. Epub 2021 Feb 25.

Department of Cardiology, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, China.

Background: Patients with coronary artery disease (CAD) are characterized by a decline in vascular regeneration, which is related to the dysfunction of endothelial progenitor cells (EPCs). G-protein-coupled receptor 4 (GPR4) is a proton-sensing G-protein-coupled receptor (GPCR) that contributes to neovascularization in acidic microenvironments. However, the role of GPR4 in regulating the angiogenic capacity of EPCs from CAD patients in response to acidity generated in ischemic tissue remains completely unclear.

Methods: The angiogenic capacity of EPCs collected from CAD patients and healthy subjects was evaluated in different pH environments. The GPR4 function of regulating EPC-mediated angiogenesis was analyzed both in vitro and in vivo. The downstream mechanisms were further investigated by genetic overexpression and inhibition.

Results: Acidic environment prestimulation significantly enhanced the angiogenic capacity of EPCs from the non-CAD group both in vivo and in vitro, while the same treatment yielded the opposite result in the CAD group. Among the four canonical proton-sensing GPCRs, GPR4 displays the highest expression in EPCs. The expression of GRP4 was markedly lower in EPCs from CAD patients than in EPCs from non-CAD individuals independent of acid stimulation. The siRNA-mediated knockdown of GPR4 with subsequent decreased phosphorylation of STAT3 mimicked the impaired function of EPCs from CAD patients at pH 6.4 but not at pH 7.4. Elevating GPR4 expression restored the neovessel formation mediated by EPCs from CAD patients in an acidic environment by activating STAT3/VEGFA signaling. Moreover, the beneficial impact of GPR4 upregulation on EPC-mediated angiogenic capacity was abrogated by blockade of the STAT3/VEGFA signaling pathway.

Conclusions: Our present study demonstrated for the first time that loss of GPR4 is responsible for the decline in proton sensing and angiogenic capacity of EPCs from CAD patients. Augmentation of GPR4 expression promotes the neovessel formation of EPCs by activating STAT3/VEGF signaling. This finding implicates GPR4 as a potential therapeutic target for CAD characterized by impaired neovascularization in ischemic tissues.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13287-021-02221-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905863PMC
February 2021

Machine Learning-Based Decision Model to Distinguish Between COVID-19 and Influenza: A Retrospective, Two-Centered, Diagnostic Study.

Risk Manag Healthc Policy 2021 15;14:595-604. Epub 2021 Feb 15.

Emergency Center, Hubei Clinical Research Center for Emergency and Resuscitation, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People's Republic of China.

Background: Considering the current situation of the novel coronavirus disease (COVID-19) epidemic control, it is highly likely that COVID-19 and influenza may coincide during the approaching winter season. However, there is no available tool that can rapidly and precisely distinguish between these two diseases in the absence of laboratory evidence of specific pathogens.

Methods: Laboratory-confirmed COVID-19 and influenza patients between December 1, 2019 and February 29, 2020, from Zhongnan Hospital of Wuhan University (ZHWU) and Wuhan No.1 Hospital (WNH) located in Wuhan, China, were included for analysis. A machine learning-based decision model was developed using the XGBoost algorithms.

Results: Data of 357 COVID-19 and 1893 influenza patients from ZHWU were split into a training and a testing set in the ratio 7:3, while the dataset from WNH (308 COVID-19 and 312 influenza patients) was preserved for an external test. Model-based decision tree selected age, serum high-sensitivity C-reactive protein and circulating monocytes as meaningful indicators for classifying COVID-19 and influenza cases. In the training, testing and external sets, the model achieved good performance in identifying COVID-19 from influenza cases with a corresponding area under the receiver operating characteristic curve (AUC) of 0.94 (95% CI 0.93, 0.96), 0.93 (95% CI 0.90, 0.96), and 0.84 (95% CI: 0.81, 0.87), respectively.

Conclusion: Machine learning provides a tool that can rapidly and accurately distinguish between COVID-19 and influenza cases. This finding would be particularly useful in regions with massive co-occurrences of COVID-19 and influenza cases while limited resources for laboratory testing of specific pathogens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/RMHP.S291498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895911PMC
February 2021

Structural characterization and statistical properties of jammed soft ellipsoid packing.

Soft Matter 2021 Mar;17(10):2963-2972

Shanghai Key Laboratory of Magnetic Resonance, Institute of Materials, School of Physics and Electronic Science, East China Normal University, Shanghai 200241, P. R. China.

The jamming transition and jammed packing structures of hydrogel soft ellipsoids are studied using magnetic resonance imaging techniques. As the packing fraction increases, the fluctuation of local free volume decreases and the fluctuation of particle deformation increases. Effective thermodynamic quantities are obtained by characterizing these fluctuations using k-gamma distributions based on an underlying statistical model for granular materials. Surprisingly, the two granular temperatures measuring the relative fluctuations of both free volume and particle deformation remain basically unchanged as the packing fraction increases. The total configurational entropy is also approximately constant for packing with different packing fractions. The significantly different behaviors of these effective thermodynamic quantities compared with hard sphere systems are further attributed to a statistically affine structural transformation of the packing structures along with particle deformations when the packing fraction changes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0sm01699cDOI Listing
March 2021

Suhuang Zhike Capsules for the Treatment of Cough Variant Asthma: A Meta-analysis.

Evid Based Complement Alternat Med 2020 31;2020:9485746. Epub 2020 Dec 31.

Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China.

Cough variant asthma (CVA) is a unique type of asthma characterized by cough as the only or primary clinical presentation. Inhaled glucocorticoid is the main treatment in clinical practice currently, but its efficacy remains relatively unsatisfactory. Traditional Chinese medicine has certain advantages in the treatment of CVA, and at present, the most commonly used traditional Chinese medicine is Suhuang Zhike Capsule (SZC). The aim of this study was to systematically evaluate the efficacy and safety of SZC in the treatment of CVA using a meta-analysis. A comprehensive search of papers published in the PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature database (CBM), Wanfang Database, and VIP Information (VIP) from January 2018 to June 2019 was conducted. Review Manager 5.3 was used to carry out a meta-analysis of 10 studies that fulfilled the inclusion criteria. In a total of 10 randomized controlled trials, 896 CVA patients were included. The results showed the following: (1) compared with conventional Western medicine, SZC can effectively increase the efficacy rate of CVA (RR 1.25, 95% CI, 1.16-1.35, < 0.00001) and (2) compared with other traditional Chinese medicines, SZC can effectively increase the efficacy rate of CVA (RR 1.44, 95% CI, 1.01-2.05, =0.05), In conclusion, our study builds on existing clinical evidence showing that SZC is safe and effective in treating CVA. However, larger randomized controlled trials are required for further validation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/9485746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790581PMC
December 2020

Surface self-assembly involving the interaction between S and N atoms.

Chem Commun (Camb) 2021 Feb 11;57(11):1328-1331. Epub 2021 Jan 11.

Key Laboratory for the Physics and Chemistry of Nanodevices and Center for Carbon-based Electronics, Department of Electronics, Peking University, Beijing 100871, China.

Controllable molecular self-assembly is vital for nanostructure construction. Here, three different self-assembling networks are realized by varying the chemical composition of the molecular building blocks of the same architecture. This is the first time that SN electrostatic attraction has been employed to regulate surface self-assembly. All molecular structures are characterized using low-temperature scanning tunnelling microscopy. The density functional theory calculations elaborate the structure formation mechanism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0cc07931fDOI Listing
February 2021

Aldolase is a sensor for both low and high glucose, linking to AMPK and mTORC1.

Cell Res 2021 Apr 21;31(4):478-481. Epub 2020 Dec 21.

State Key Laboratory for Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, 361102, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41422-020-00456-8DOI Listing
April 2021

[Effect of cochlear implantation on tinnitus and the prognosis mode analysis].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2020 Nov;34(11):966-971

Department of Otolaryngology,Wuhan Union Hospital,Tongji Medical College of Huazhong University of Science and Technology,Wuhan,430022,China.

To describe the effects of the possible related factors in unilateral cochlear implantation(CI) on tinnitus,and analysis the hearing and speech ability in different tinnitus prognosis mode. The 70 post-lingual deafness CI patients(27.73±14.032 years old) in the clinical trial for LCI-20PI cochlear implant and LSP-20A sound processor project by a fast questionnaire about the tinnitus positive or negative respectively before the CI, 3rd, 6th, 9th and 12th months after the first mapping. 6 modes about tinnitus development were record: Type A(-to-), no tinnitus before the CI and continued negative until the last follow-up; Type B(+ to-), have tinnitus before CI and disappeared after the mapping; Type C(-to +), no tinnitus before but appeared after the surgery; Type D(+ to-to +), have tinnitus before the CI and disappeared during the continue follow-up, but finally the tinnitus show up again at last; Type E(-to + to-), no tinnitus before and suffered from tinnitus after the CI surgery, but the noise disappeared at last; Type F(+ to +), have the tinnitus in all the duration. Then we briefly analyzed the factors like age, gender, the duration of hearing loss, and the duration of hearing aids usage. Compare the characteristics in all the modes of tinnitus prognosis. In this research CI treatment effect rate on tinnitus is 80%. The mean age of Type A (tinnitus from -to- ) group is (20.79 ±11.364) years old; Type B (tinnitus from + to-) group is (32.69±10.606) years old; Type C(tinnitus from-to +) group is (40.25±2.217) years old; Type D(tinnitus from + to-to +) group is (28.00±0) years old; Type E (tinnitus from-to + to-) group is (52.50±6.364) years old; Type F (tinnitus from + to +) group is (30.33±11.015) years old. And <0.05 between the groups, while the severe-deaf-duration intergroup differences (>0.05). The mean speech discrimination rates are all elevate after 12 months and no statistical significance between the groups. But the E group has a lowst elevation in mean pure tone threshold (22.50±3.535 ) dB HL, when the F group has the best promotion (56.04±10.649 ) dB HL, and the difference between the groups is statistically significant. The cochlear implantation could eliminate tinnitus in 80% patients in this research. The better elevation of hearing and speech ability in the patients with persist tinnitus pre-and post-CI usage may related to amount and functions of the residual auditory nerves. Age may be an important factor in tinnitus generation, which may need more explanation and attention during the rehabilitation period.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.13201/j.issn.2096-7993.2020.11.002DOI Listing
November 2020

Circulating senescent angiogenic T cells are linked with endothelial dysfunction and systemic inflammation in hypertension.

J Hypertens 2021 May;39(5):970-978

Department of Hypertension and Vascular Disease, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou.

Objective: Angiogenic T cells (Tang cells), a recently discovered T-cell subset, have been reported involved in the repair of endothelial injury. The purpose of this study was to explore the correlation of immunologic senescence and pro-inflammatory capacity of Tang cells with endothelial dysfunction in hypertensive patients.

Methods: Immunological characteristics of Tang cells (CD3+CD31+CXCR4+) from hypertensive patients with or without endothelial dysfunction were elucidated by surface immunophenotyping and intracellular cytokine staining. Endothelial function was measured by flow-mediated dilation (FMD).

Results: The frequency of CD28null subset in CD4+ Tang cells was notably elevated in hypertensive patients with endothelial dysfunction, which was negatively associated with FMD. The high frequency of CD28nullCD4+ Tang cells was an independent risk factor of endothelial dysfunction with good diagnostic performance in ROC curve analysis. Immunophenotyping revealed that this specific subset of Tang cells exhibited senescent profile and has low hTERT expression. CD28nullCD4+ Tang cells produced high levels of inflammatory cytokines, IL-6, IFN-γ and TNF-α, and significantly correlated with the systemic inflammation in hypertensive patients with endothelial dysfunction.

Conclusion: Collectively, our findings demonstrate for the first time that CD28null subset in CD4+ Tang cells with senescent and pro-inflammatory phenotype is dependently correlated with impaired FMD and systemic inflammation, which might contribute to the immunopathologic mechanism of endothelial dysfunction. Identification of a pathogenic CD4+ Tang-cell subset lacking CD28 may offer opportunities for the evaluation and management of endothelial dysfunction in hypertension.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/HJH.0000000000002715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048736PMC
May 2021

Our Experiences with Plastic and Reconstructive Surgery Procedures during Coronavirus Disease 2019 Pandemic.

Plast Reconstr Surg Glob Open 2020 May 13;8(5):e2868. Epub 2020 May 13.

Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

The novel Coronavirus Disease 2019 (COVID-19) has rapidly become a health threat worldwide and has been declared global pandemic by the World Health Organization. Possible transmission routes, including respiratory droplets, close contact, and aerosol propagation, have put plastic and reconstructive healthcare professionals at high risk, especially during surgical procedures. The aim of this study was to summarize and share our experience of infection control measures and corresponding outcomes during the COVID-19 pandemic.

Methods: Infection control measures, including workflow optimization, useful epidemiologic survey methods, and personal full protective clothing, were discussed. Characteristics and outcomes of emergency cases and elective cases under local and general anesthesia during the COVID-19 pandemic were summarized.

Results: A hierarchy of interventions were applied mainly from 4 aspects. First, administration control and online consultation significantly decreased patient attendance. Second, a triage workflow was established to identify high-/low-risk patients, with clinical manifestations (fever, fatigue, cough, nasal discharge, etc), epidemiologic survey, blood test, chest computed tomographic scan, and coronavirus test if necessary. Third, strict environmental control was adopted using increasing ventilation, isolated room for inpatients, etc. Fourth, proper rotation of healthcare staff was ensured to reduce workload and minimize possible contact. A total of 904 emergency interventions, 2561 local anesthesia, and 570 general anesthesia were performed during this period, and none of the cases/healthcare professionals were found to be infected.

Conclusions: Our experience could help global plastic and reconstructive healthcare professionals to get better preparation and continue to give qualified medical services during the COVID-19 pandemic. Proper adjustments should be taken according to their own clinical settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/GOX.0000000000002868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572092PMC
May 2020

Combined Treatment of Non-Small-Cell Lung Cancer Using Shenyi Capsule and Platinum-Based Chemotherapy: A Meta-Analysis and Systematic Review.

Evid Based Complement Alternat Med 2020 13;2020:3957193. Epub 2020 Oct 13.

Department of Physiology, Xuzhou Medical University, Xuzhou 221009, China.

Background: The efficacy and safety of combined treatment of non-small-cell lung cancer (NSCLC) using Shenyi capsules and platinum-based chemotherapy were comprehensively evaluated.

Methods: A computer-based search was used to identify reports on clinical randomized controlled trials (RCTs) on this combined treatment for NSCLC from the PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP, China Biomedical (CBM), and Wanfang Data electronic databases. The databases were searched from their start to February 2020. The quality of the included studies was evaluated and then crosschecked by two independent evaluators. A meta-analysis was conducted using RevMan5.3.

Results: A total of 27 RCTs involving 2,663 patients were included in the meta-analysis, including 1,380 and 1,283 patients in the treatment and control groups, respectively. The results of the meta-analysis showed that, compared to platinum-based chemotherapy alone, the 1-year survival rate (relative risk (RR) = 1.27, 95% confidence interval (CI) [1.10, 1.47], < 0.01), 2-year survival rate (RR = 1.35, 95% CI [1.10, 1.65], < 0.01), objective tumour remission rate (RR = 1.52, 95% CI [1.35, 1.71], < 0.01), and body CD4/CD8 ratio (standardized mean difference (SMD) = 0.12, 95% CI [0.07, 0.17], < 0.01) were increased for the combined treatment of NSCLC using Shenyi capsules and platinum-based chemotherapy; moreover, quality of life was also improved (RR = 2.09, 95%CI [1.75, 2.50], < 0.01) and it reduced leukocyte toxicity (RR = 0.49, 95%CI [0.39, 0.63], < 0.01), haemoglobin toxicity (RR = 0.48, 95% CI [0.28, 0.81], < 0.01), platelet toxicity (RR = 0.44, 95% CI [0.28, 0.70], < 0.01), vomiting reaction (RR = 0.60, 95% CI [0.45, 0.78], < 0.01), and serum vascular endothelial growth factor level (SMD = -63.67, 95% CI [-67.59, -59.75], < 0.01).

Conclusions: The treatment of NSCLC using Shenyi capsules together with routine platinum-based chemotherapy could enhance short- and long-term efficacy, improve patient quality of life, alleviate toxicity and side-effects of platinum-based chemotherapeutic drugs, boost body immune function, and inhibit tumour neovascularisation. These findings require further validation in large-sample, high-quality RCTs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/3957193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578725PMC
October 2020

Bifunctional macromolecule activating both OX40 and interferon-α signaling displays potent therapeutic effects in mouse HBV and tumor models.

Int Immunopharmacol 2020 Dec 19;89(Pt B):107099. Epub 2020 Oct 19.

Nanjing U-Mab Biopharma Co., Ltd, 699-8 Xuanwu Avenue, Nanjing, Jiangsu 210042, PR China. Electronic address:

Combinatory enhancement of innate and adaptive immune responses is a promising strategy in immunotherapeutic drug development. Bifunctional macromolecules that simultaneously target two mechanisms may provide additional advantages over the combination of targeting two single pathways. Interferon alpha (IFNα) has been used clinically against viral infection such as the chronic infection of hepatitis B virus (CHB) as well as some types of cancers. OX40 is a costimulatory immune checkpoint molecule involved in the activation of T lymphocytes. To test whether simultaneously activating IFNα and OX40 signaling pathway could produce a synergistic therapeutic effect on CHB and tumors, we designed a bifunctional fusion protein composed of a mouse OX40 agonistic monoclonal antibody (OX86) and a mouse IFNα4, joined by a flexible (GGGGS) linker. This fusion protein, termed OX86-IFN, can activate both IFNα and OX40. We demonstrated that OX86-IFN could effectively activate T lymphocytes in the peripheral blood of mice. Furthermore, we showed that OX86-IFN had superior therapeutic effect to monotherapies in HBV hydrodynamic transfection and syngeneic tumor models. Collectively, our data suggests that simultaneously targeting interferon and OX40 signaling pathways by bifunctional molecule OX86-IFN elicits potent antiviral and antitumor activities, which could provide a new strategy in developing therapeutic agents against viral infection and tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2020.107099DOI Listing
December 2020

Chronic cold exposure enhances glucose oxidation in brown adipose tissue.

EMBO Rep 2020 11 12;21(11):e50085. Epub 2020 Oct 12.

Department of Molecular & Cellular Endocrinology, Diabetes and Metabolism Research Institute, City of Hope Medical Center, Duarte, CA, USA.

The cultured brown adipocytes can oxidize glucose in vitro, but it is still not fully clear whether brown adipose tissue (BAT) could completely oxidize glucose in vivo. Although positron emission tomography (PET) with F-fluorodeoxyglucose ( F-FDG) showed a high level of glucose uptake in the activated BAT, the non-metabolizable F-FDG cannot fully demonstrate intracellular glucose metabolism. Through in vivo [U- C]glucose tracing, here we show that chronic cold exposure dramatically activates glucose oxidation in BAT and the browning/beiging subcutaneous white adipose tissue (sWAT). Specifically, chronic cold exposure enhances glucose flux into the mitochondrial TCA cycle. Metabolic flux analysis models that β3-adrenergic receptor (β3-AR) agonist significantly enhances the flux of mitochondrial pyruvate uptake through mitochondrial pyruvate carrier (MPC) in the differentiated primary brown adipocytes. Furthermore, in vivo MPC inhibition blocks cold-induced glucose oxidation and impairs body temperature maintenance in mice. Together, mitochondrial pyruvate uptake and oxidation serve an important energy source in the chronic cold exposure activated BAT and beige adipose tissue, which supports a role for glucose oxidation in brown fat thermogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15252/embr.202050085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645266PMC
November 2020

Huisheng Oral Solution Adjunct With Platinum-Based Chemotherapy for the Treatment of Advanced Non-Small Cell Lung Cancer: A Meta-Analysis and Systematic Review.

Front Pharmacol 2020 8;11:476165. Epub 2020 Sep 8.

Department of Respiratory Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.

Background: Platinum-based chemotherapy is one of the first line therapies for the advanced non-small cell lung cancer (NSCLC), even though its high toxicity and limited clinical effects cannot be neglected. Huisheng oral solution (HSOS) has been widely used as an adjuvant chemotherapy drug for NSCLC in China. To systematically analyze the therapeutic effects of the combination of HSOS and platinum-based chemotherapy, a comprehensive meta-analysis was performed.

Objectives: This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of HSOS for NSCLC.

Methods: The randomized controlled trials (RCTs) were selected on seven medical databases up to June 2020, including advanced NSCLC treatment using HSOS plus platinum-based chemotherapy versus chemotherapy alone. We followed the PRISMA checklist in general, applying Cochrane handbook 5.1.0, GRADE Pro GDT, RevMan 5.3, Stata12.0, and TSA 0.9.5.10 Beta to evaluate the quality of the study and analyze the data.

Results: Based on Cochrane handbook 5.1.0, 15 RCTs consisting 1165 patients met the criteria and were selected for further analysis. Compared to chemotherapy alone, the chemotherapy combined with HSOS significantly improved objective tumor response (ORR) [RR = 1.38, 95% CI (1.19, 1.59), < 0.0001], disease control rate (DCR) [RR = 1.10, 95% CI (1.04, 1.16), = 0.0006], and Karnofsky performance status (KPS) [RR = 1.79, 95% CI (1.41, 2.26), < 0.00001]. However, there was no evidence of improvement in the 1-year survival rate [RR = 1.37, 95% CI (0.98, 1.92), = 0.07]. In terms of the side effects, HSOS administered concurrently with chemotherapy resulted in a serial of substantial benefits: lower toxicity to white blood cell [RR = 0.30, 95% CI (0.20, 0.43), < 0.00001], lower platelet toxicity [RR = 0.56, 95% CI (0.34, 0.92), = 0.02], and reduced incidence of vomiting [RR = 0.52, 95% CI (0.29, 0.92), = 0.03].

Conclusions: The meta-analysis indicated that HSOS plus platinum-based chemotherapy was more beneficial for patients, as the therapy could synergize antitumor activity and could attenuate toxicity. The finding requires confirmation by further rigorously designed RCTs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2020.476165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508161PMC
September 2020

YTHDF2 correlates with tumor immune infiltrates in lower-grade glioma.

Aging (Albany NY) 2020 Sep 27;12(18):18476-18500. Epub 2020 Sep 27.

Department of Cancer Chemotherapy, Zengcheng District People's Hospital of Guangzhou, Guangzhou 511300, China.

Immunotherapy is an effective treatment for many cancer types. However, YTHDF2 effects on the prognosis of different tumors and correlation with tumor immune infiltration are unclear. Here, we analyzed The Cancer Genome Atlas and Gene Expression Omnibus data obtained through various web-based platforms. The analyses showed that YTHDF2 expression and associated prognoses may depend on cancer type. High YTHDF2 expression was associated with poor overall survival in lower-grade glioma (LGG). In addition, YTHDF2 expression positively correlated with expression of several immune cell markers, including PD-1, TIM-3, and CTLA-4, as well as tumor-associated macrophage gene markers, and isocitrate dehydrogenase 1 in LGG. These findings suggest that YTHDF2 is a potential prognostic biomarker that correlates with LGG tumor-infiltrating immune cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.103812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585119PMC
September 2020

Correction to: CD103-positive CSC exosome promotes EMT of clear cell renal cell carcinoma: role of remote MiR-19b-3p.

Mol Cancer 2020 Sep 24;19(1):144. Epub 2020 Sep 24.

Department of Urology (Heilongjiang Key Laboratory of Scientific Research in Urology), the Fourth Hospital of Harbin Medical University, No. 37 Yi-Yuan Street, Nangang District, Harbin, Heilongjiang Province, 150081, People's Republic of China.

An amendment to this paper has been published and can be accessed via the original article.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12943-020-01261-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7513539PMC
September 2020

Preparation and Photoluminescent Properties of Three 5-Amino Benzothiadiazoles (5-amBTDs).

Chem Asian J 2020 Nov 29;15(21):3519-3526. Epub 2020 Sep 29.

Department of Chemistry, Zhejiang University, Hangzhou, P. R. China.

Three D-A compounds were designed and synthesized based on a benzothiadiazole acceptor. Azepane (AP), iminodubenzyl (IDB) and iminostilbene (ISB) were used, respectively, as donors and installed on the 5-position of BTD to afford 1, 2 and 3, respectively. Their photophysical properties in different states (solution, film, crystal, and powder) are systematically investigated. Among them, AIE-active compounds 2 and 3 were found to have good sensitivity toward viscosity and display quite good linear relationship with an increase in viscosity. Compound 2 displayed dual emission in solutions which largely depended on the polarity of the solvent. Meanwhile, compound 2 exhibits a mechanochromic character with disappearance and reappearance of a dual-emissive peak induced by mechanical grinding and solvent fuming. Furthermore, these three compounds can be used in the fabrication of blue OLED devices.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/asia.202000980DOI Listing
November 2020

Potential mechanism underlying the effect of matrine on COVID-19 patients revealed through network pharmacological approaches and molecular docking analysis.

Arch Physiol Biochem 2020 Sep 11:1-8. Epub 2020 Sep 11.

Department of Physiology, Xuzhou Medical University, Xuzhou, China.

Background: The clinical efficacy of matrine in treating coronavirus disease (COVID-19) has been confirmed; however, its underlying mechanism of action remains unknown.

Methods: TCMSP, SwissTargetPrediction, SEA, GeneCards, CTD, and TTD were used to identify potential targets for matrine in SARS-CoV-2. Cytoscape software was used to determine the target-pathway network for topographical analysis. The online STRING analysis platform and Cytoscape were together used to generate a PPI network and for GO and KEGG pathway enrichment analysis. Finally, molecular docking simulations were performed to study matrine-Mpro, matrine-ACE2, and matrine-RdRp interactions.

Results: Ten common matrine targets were obtained, particularly including TNF-α, IL-6, and CASP3. GO and KEGG pathway enrichment analysis revealed five significantly enriched signalling pathways involved in cell proliferation, apoptosis, programmed cell death, and immune responses.

Conclusions: During COVID-19 treatment, matrine regulates viral replication, host cell apoptosis, and inflammation by targeting the TNF-α, IL-6, and CASP3 in the TNF signalling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13813455.2020.1817944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544918PMC
September 2020

Allisartan Isoproxil Improves Endothelial Function and Vascular Damage in Patients with Essential Hypertension: A Single-Center, Open-Label, Randomized Controlled Trial.

Adv Ther 2020 08 24;37(8):3551-3561. Epub 2020 Jun 24.

Department of Hypertension and Vascular Disease, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.

Introduction: Allisartan isoproxil is a novel angiotensin II type 1 receptor antagonist that has been confirmed to lower blood pressure and protect target organs effectively. However, its role in improving endothelial function and vascular damage has not been investigated yet.

Methods: Patients with initially diagnosed mild essential hypertension (BP ranging from 140/90 to 159/99 mmHg) with age from 25-75 years were randomly assigned 1:1 to either the allisartan group (allisartan 240 mg/day and lifestyle modification) or the lifestyle modification group and were followed up for 30 days. Flow-mediated dilation (FMD), brachial-ankle pulse wave velocity (baPWV) and endothelial microparticles (EMPs) were measured for evaluation of endothelial function and vascular damage. In addition, we enrolled 36 normotensive individuals as healthy control.

Results: Seventy-two mildly hypertensive patients were enrolled in this study. After 30 days of treatment, a significant increase in FMD was observed in the allisartan group (0.9 ± 0.7%, p < 0.001) and remained unchanged in the lifestyle modification group, but the difference between the two groups did not reach statistical significance (p = ns). EMPs, baPWV, SBP and DBP decreased by 251.0 ± 255.9 counts/μl (p < 0.001), 102.8 ± 84.2 cm/s (p < 0.001), 13.20 ± 3.9 mmHg (p < 0.001) and 9.35 ± 2.5 mmHg (p < 0.001), respectively, in the allisartan group, while by 21.3 ± 84.3 counts/μl (p = ns), 0.4 ± 22.0 cm/s (p = ns), 3.2 ± 6.0 mmHg (p < 0.01) and 1.0 ± 2.5 mmHg (p = ns), respectively, in the lifestyle modification group. All of the indexes above achieved statistical significance between the allisartan and lifestyle modification groups (p < 0.05). Besides, after 30 days of allisartan administration baPWV and EMPs were comparable to those measured in the healthy control group, while the difference in SBP, DBP and FMD remained significant between the allisartan and healthy control groups (p < 0.05).

Conclusion: The present study demonstrates for the first time that allisartan isoproxil exerts a favorable effect on improving endothelial function and vascular damage in patients with mild EH, making it a promising drug for management of EH.

Clinical Trial Registration: ChiCTR2000032332.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12325-020-01413-yDOI Listing
August 2020

Comparative Transcriptome Profiling Analysis Uncovers Novel Heterosis-Related Candidate Genes Associated with Muscular Endurance in Mules.

Animals (Basel) 2020 Jun 4;10(6). Epub 2020 Jun 4.

College of Animal Science and Technology, Northwest A&F University, Yangling, Xianyang 712100, China.

Heterosis has been widely exploited in animal and plant breeding programs to enhance the productive traits of hybrid progeny from two breeds or species. However, its underlying genetic mechanisms remain enigmatic. Transcriptome profiling analysis can be used as a method for exploring the mechanism of heterosis. Here, we performed genome-wide gene expression and alternative splicing (AS) analyses in different tissues (muscle, brain, and skin) from crosses between donkeys and horses. Our results indicated that 86.1% of the differentially expressed genes (DEGs) and 87.2% of the differential alternative splicing (DAS) genes showed over-dominance and dominance in muscle. Further analysis showed that the "muscle contraction" pathway was significantly enriched for both the DEGs and DAS genes in mule muscle tissue. Taken together, these DEGs and DAS genes could provide an index for future studies of the genetic and molecular mechanism of heterosis in the hybrids of donkey and horse.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ani10060980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341310PMC
June 2020

Effectiveness of fat suppression using a water-selective binomial-pulse excitation in chemical exchange saturation transfer (CEST) magnetic resonance imaging.

MAGMA 2020 Dec 27;33(6):809-818. Epub 2020 May 27.

Shanghai Key Laboratory of Magnetic Resonance, School of Physics and Electronic Science, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062, China.

Purpose: The purpose of this study was to characterize the individual contribution of multiple fat peaks to the measured chemical exchange saturation transfer (CEST) signal when using water-selective binomial-pulse excitation and to determine the effects of multiple fat peaks in the presence of B inhomogeneity.

Methods: The excitation profiles of multiple binomial pulses were simulated. A CEST sequence with binomial-pulse excitation and modified point-resolved spectroscopy localization was then applied to the in vivo lumbar spinal vertebrae to determine the signal contributions of three distinct groups of lipid resonances. These confounding signal contributions were measured as a function of the irradiation frequency offset to determine the effect of the multi-peak nature of the fat signal on CEST imaging of exchange sites (at 1.0, 2.0 and 3.5 ppm) and robustness in the presence of B inhomogeneity.

Results: Numerical simulations and in vivo experiments showed that water excitation (WE) using a 1-3-3-1 (WE-4) pulse provided the broadest signal suppression, which provided partial robustness against B inhomogeneity effects. Confounding fat signal contributions to the CEST contrasts at 1.0, 2.0 and 3.5 ppm were unavoidable due to the multi-peak nature of the fat signal. However, these CEST sites only suffer from small lipid artifacts with ∆B spanning roughly from  - 50 to 50 Hz. Especially for the CEST site at 3.5 ppm, the lipid artifacts are smaller than 1% with ∆B in this range.

Conclusion: In WE-4-based CEST magnetic resonance imaging, B inhomogeneity is the limiting factor for fat suppression. The CEST sites at 1.0, 2.0 ppm and 3.5 ppm unavoidably suffer from lipid artifacts. However, when the ∆B is confined to a limited range, these CEST sites are only affected by small lipid artifacts, which may be ignorable in some cases of clinical applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10334-020-00851-7DOI Listing
December 2020

Effect of CaO on Pyrolysis Products and Reaction Mechanisms of a Corn Stover.

ACS Omega 2020 May 30;5(18):10276-10287. Epub 2020 Apr 30.

Engineering Research Centre of Oil Shale Comprehensive Utilization, Ministry of Education, Northeast Electric Power University, Jilin City, Jilin 132012, PR China.

To better realize how CaO promoted the pyrolysis process of a corn stover, which was important for further development of its technology, various effects of calcium oxide (CaO) on the pyrolysis of the corn stover at different temperatures were studied. The pyrolysis of the corn stover mainly occurred at 90, 291, 335, and 385 °C, which were correspondent to the pyrolysis temperatures of water, hemicellulose, cellulose, and lignin, respectively. Moreover, CaO was found to absorb some CO and HO produced during the pyrolysis, as well as promote the occurrence of pyrolysis, and reduce the activation energy required for the reaction. According to the calculation of the activation energy, the optimal addition ratio of CaO and the corn stover should be between 1:2 and 1:1. The analysis of the release of pyrolysis gas showed that CaO had a beneficial effect on deacidification and the production of hydrocarbons and aromatic compound gas. When the addition ratio was 1:1, the release amount of the acidic substance was the lowest. When the ratio of CaO and the corn stover was 1:2, the release amount of HO, CO, and aromatic rings was at the maximum. The change of content of tri-state products generated during pyrolysis at different final temperatures was also studied by the pyrolysis experiment. The changes of functional groups in char were observed by Fourier-transform infrared spectroscopy. The results showed that with the addition of CaO, the content of HO in char, and the absorption of CO increased, which generated alkaline substances, while reacting with acidic substances, and the thermal decomposition of acidic substances in the corn stover was promoted, which caused the pyrolysis reaction of the corn stover to occur in the positive direction. With the increase of pyrolysis temperature, phenol and carboxylic acid became thermally resolved or neutralized. When the catalyst amount or temperature was gradually increased, the aliphatic group was steadily pyrolyzed while char increasingly became aromatized. Based on the comprehensive analysis of the above experimental results, it was believed that the optimal addition ratio of CaO and the corn stover should be between 1:2 and 1:1.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsomega.9b03945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226874PMC
May 2020

Association of methylenetetrahydrofolate reductase (MTHFR) variant C677T and risk of carotid atherosclerosis: a cross-sectional analysis of 730 Chinese Han adults in Chongqing.

BMC Cardiovasc Disord 2020 05 13;20(1):222. Epub 2020 May 13.

Health Management Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Background: Uncertainty still remains on the correlation of methylenetetrahydrofolate reductase (MTHFR) variant C677T with risk of carotid atherosclerosis (CAS), and there is a lack of reports on C677T/MTHFR in the Asian population. The association of C677T/MTHFR polymorphisms with CAS in the Chinese Han population in Chongqing was investigated in the present study.

Methods: Subjects (n = 730, 214 females and 516 males, Han ethnicity) who provided an informed consent were randomly selected from the general population of Chongqing, China. Polymerase chain reaction-restriction fragment length polymorphism and Sanger sequencing genotyping assays were used to determine the MTHFR genotypes. The atherosclerosis index of the intima-media thickness (IMT) was measured by high-resolution ultrasound to evaluate the CAS. Less than 1.0 mm was considered as normal for IMT, 1.0-1.5 mm was considered as thickening, and ≥ 1.5 mm and a local bulge thickened in the lumen was considered as CAS. According to the carotid ultrasonography results, these subjects were divided into two groups: CAS-group (IMT ≥ 1.0 mm) and control group (IMT < 1.0 mm).

Results: The frequency of C/T heterozygotes, T/T homozygotes genotype was significantly higher in the subjects with CAS (62% vs. 36.9%; 16.2% vs. 9.5%; 47.2% vs. 27.9%, P < 0.05), while the frequency of C/C homozygotes and C allele was significantly lower (21.8% vs. 53.7%; 52.8% vs. 72.1%, P < 0.05), when compared to the control group. The risk of CAS was higher for subjects with C/T heterozygotes and T/T homozygotes (OR = 4.06, 95% CI: 2.76-5.98, P < 0.001 and OR = 3.14, 95% CI: 1.73-5.69, P < 0.001, respectively), when compared to the subjects with the C/C genotype. In the model 1 (CT + TT versus CC), C677T/MTHFR was significantly associated with the prevalence of CAS, and the all adjusted OR values for CAS were 3.87 (95% CI, 2.67 to 5.62) in all, 17.18 (95% CI, 7.27 to 40.49) in women and 2.57 (95% CI, 1.65 to 3.99) in men after adjusting for potential confounding factors.

Conclusions: The present study suggests that a mutation in the methylenetetrahydrofolate reductase gene is a risk factor of CAS in the Chinese Han population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12872-020-01505-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222312PMC
May 2020

Comprehensive analysis of long non‑coding RNA using an associated competitive endogenous RNA network in Wilms tumor.

Mol Med Rep 2020 Jul 5;22(1):105-116. Epub 2020 May 5.

Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China.

Wilms tumor (WT) is the most common malignant renal neoplasm in children; however, the underlying molecular mechanisms are not well understood. According to the competing endogenous RNA (ceRNA) theory, long non‑coding RNAs (lncRNAs) can regulate the expression of target genes by adsorbing microRNAs (miRNAs/miRs). However, the role of lncRNAs in WT has not been fully elucidated. The aim of the present study was to construct a ceRNA network to identify the potential lncRNAs involved in WT. The expression profiles of lncRNAs, miRNAs and mRNAs in 120 WT and six normal tissues were obtained from the Therapeutically Applicable Research to Generate Effective Treatments database. A total of 442 lncRNAs, 214 miRNAs and 4,912 mRNAs were identified as differentially expressed in WT and were enriched in 472 Gene Ontology terms (355 biological processes, 89 cellular components and 29 molecular functions) and 18 Kyoto Encyclopedia of Genes and Genomes pathways. A lncRNA‑miRNA‑mRNA ceRNA network of WT consisting of with 32 lncRNAs, 14 miRNAs and 158 mRNAs was constructed, based on the bioinformatics analysis of the miR target prediction database and the miRNAcode, miRTarBase and TargetScan databases. Subsequently, three lncRNAs, three miRNAs and 17 mRNAs, which had a significant effect on the overall survival rate of patients with WT, were identified based on the survival analysis. The three lncRNAs were also differentially expressed in the late and early stages of WT and were validated using the GSE66405 dataset obtained from the Gene Expression Omnibus database. In conclusion, the present study generated a specific lncRNA‑related ceRNA network of WT, which may provide a novel perspective on the molecular mechanisms underlying the progression and prognosis of the disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mmr.2020.11124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252721PMC
July 2020

The role of macrophages in the formation of hypertrophic scars and keloids.

Burns Trauma 2020 11;8:tkaa006. Epub 2020 Mar 11.

Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200011, China.

Numerous studies have shown that macrophages can orchestrate the microenvironment from the early stage of wound healing to the later stages of scar formation. However, few reviews have highlighted the significance of macrophages during the formation of abnormal scars. The purpose of this review was to outline the polarization of macrophages from early to late stage of pathological scar formation, focusing on spatiotemporal diversity of M1 and M2 macrophages. In this review, the role of macrophages in the formation of hypertrophic scars and keloids is summarized in detail. First, an increased number of M2 cells observed before injuries are significantly associated with susceptibility to abnormal scar pathogenesis. Second, decreased expression of M1 at the early stage and delayed expression of M2 at the late stage results in pathological scar formation. Third, M2 cells are highly expressed at both the margin and the superficial region, which is consistent with the invasive property of keloids. Finally, this review helps to characterize strategies for the prediction and prevention of pathological scar formation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/burnst/tkaa006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175772PMC
March 2020

Switching from Fatty Acid Oxidation to Glycolysis Improves the Outcome of Acute-On-Chronic Liver Failure.

Adv Sci (Weinh) 2020 Apr 13;7(7):1902996. Epub 2020 Feb 13.

Department of Pharmacy The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052 China.

Acute-on-chronic liver failure (ACLF) has a high mortality rate. Metabolic reprogramming is an important mechanism for cell survival. Herein, the metabolic patterns of ACLF patients are analyzed. An in vitro model of ACLF is established using Chang liver cells under hyperammonemia and hypoxia. A randomized clinical trial (ChiCTR-OPC-15006839) is performed with patients receiving -ornithine and -aspartate (LOLA) daily intravenously (LOLA group) and trimetazidine (TMZ) tid orally (TMZ group) based on conventional treatment (control group). The primary end point is 90-day overall survival, and overall survival is the secondary end point. By analyzing metabolic profiles in liver tissue samples from hepatitis B virus (HBV)-related ACLF patients and the controls, the metabolic characteristics of HBV-related ACLF patients are identified: inhibited glycolysis, tricarboxylic acid cycle and urea cycle, and enhanced fatty acid oxidation (FAO) and glutamine anaplerosis. These effects are mainly attributed to hyperammonemia and hypoxia. Further in vitro study reveals that switching from FAO to glycolysis could improve hepatocyte survival in the hyperammonemic and hypoxic microenvironment. Importantly, this randomized clinical trial confirms that inhibiting FAO using TMZ improves the prognosis of patients with HBV-related ACLF. In conclusion, this study provides a practical strategy for targeting metabolic reprogramming using TMZ to improve the survival of patients with HBV-related ACLF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/advs.201902996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141014PMC
April 2020

The oncogenic role of REG γ is exerted by activating the Wnt/β-catenin signaling pathway in osteosarcoma.

Am J Transl Res 2020 15;12(2):563-573. Epub 2020 Feb 15.

Department of Orthopedics, The Fourth Affiliated Hospital of Harbin Medical University Harbin, Heilongjiang Province, China.

Background: Proteasome activator γ (REG γ) expression was found to be upregulated and to play critical roles in several cancers. However, the effect of REG γ on osteosarcoma (OS) remains unclear. The objective of the present study was to explore the clinical significance of REG γ and its function in regulating the progression of OS.

Methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blotting (WB) and immunohistochemistry (IHC) analyses were performed to detect the expression levels of REG γ in OS tissues and cell lines. Then, the effects of REG γ expression on OS cell behavior were analyzed by Cell Counting Kit-8 (CCK-8), ethylene deoxyuridine (EdU), colony formation, flow cytometry, wound healing and transwell assays. The protein and mRNA levels of components involved in the Wnt/β-catenin pathway were evaluated using WB and qRT-PCR, respectively.

Results: We found that REG γ expression was significantly upregulated in both OS tissues and cell lines. Our assay results confirmed that knockdown of REG γ inhibited cell proliferation, migration, and invasion and induced apoptosis and cell cycle arrest in OS. Additionally, through WB and qRT-PCR analyses, we found that REG γ depletion markedly decreased the β-catenin, cyclin D1 and c-myc expression levels and increased the GSK-3β expression levels in OS cell lines.

Conclusions: Our results revealed that REG γ plays an oncogenic role in OS by activating the Wnt/β-catenin pathway, indicating that REG γ may be a promising therapeutic target for OS patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061849PMC
February 2020

A five-gene signature derived from m6A regulators to improve prognosis prediction of neuroblastoma.

Cancer Biomark 2020 ;28(3):275-284

Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin, China.

Background And Objective: N6-methyladenosine (m6a) is the most abundant form of methylated modification in eukaryotic mRNA. However, the role of m6A-related genes in neuroblastoma (NB), one of the most common paediatric malignant tumours, is not well known. This study aimed to determine the prognostic role of m6A-related genes in neuroblastoma.

Methods: We analysed the expression of 20 published m6A methylation regulators in 498 patients with NB from the Gene Expression Omnibus database. To determine the independent prognostic factors, we used univariate Cox analysis, the least absolute shrinkage and selection operator (LASSO) regression. The multivariate Cox analysis was used to construct a prognostic risk prediction model. 120 NB tissues from "Therapeutically Applicable Research To Generate Effective Treatments" (TARGET ) database was used to test the prognostic value. Gene set enrichment analysis was performed to discover the potential biological function of the m6A signature.

Results: The risk prediction model consisted of five genes (METT14, WTAP, HNRNPC, YTHDF1 and IGF2BP2). The receiving operating characteristic curve showed the high exactitude of the risk model. Cox regression analysis revealed that the risk model was an independent prognostic factor of overall survival. These results were reproduced using another published independent dataset. Further functional enrichment analysis suggested the involvement of the 5-gene signature in several malignancies.

Conclusion: The five m6A regulatory genes identified in this study enable clinical prognosis of NB and may serve as novel therapeutic targets for NB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/CBM-191196DOI Listing
January 2021