Publications by authors named "Ying Chen"

4,079 Publications

  • Page 1 of 1

Highly Potent and Selective Butyrylcholinesterase Inhibitors for Cognitive Improvement and Neuroprotection.

J Med Chem 2021 May 11. Epub 2021 May 11.

School of Pharmacy, China Pharmaceutical University, Nanjing 211198, People's Republic of China.

Butyrylcholinesterase (BChE) has been considered as a potential therapeutic target for Alzheimer's disease (AD) because of its compensation capacity to hydrolyze acetylcholine (ACh) and its close association with Aβ deposit. Here, we identified (BChE IC = 16 nM) and (BChE IC = 25 nM) as highly effective and selective BChE inhibitors, which were proved to be safe and long-acting. Candidate compounds exhibited neuroprotective effects and the ability to improve cognition in scopolamine- and Aβ peptide-induced cognitive deficit models. The best candidate increased the level of ghrelin, a substrate of BChE, which can function as improving the mental mood appetite. The weight gain of the -treated group remarkably increased. Hence, BChE inhibition not only plays a protective role against dementia but also exerts a great effect on treating and nursing care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jmedchem.1c00167DOI Listing
May 2021

[Expression and function analysis of FaCO gene in Festuca arundinacea].

Sheng Wu Gong Cheng Xue Bao 2021 Apr;37(4):1324-1333

Guizhou Institute of Prataculture, Guizhou Academy of Agricultural Sciences, Guiyang 550006, Guizhou, China.

Photoperiod plays an important role in transformation from vegetative growth to reproductive growth in plants. CONSTANS (CO), as a unique gene in the photoperiod pathway, responds to changes of day length to initiate flowering in the plant. In this study, the expression level of FaCONSTANS (FaCO) gene under long-day, short-day, continuous light and continuous darkness conditions was analyzed by real-time quantitative PCR. We constructed the over-expression vector p1300-FaCO and infected into Arabidopsis thaliana by Agrobacterium-mediated method. We constructed the silencing vector p1300-FaCO-RNAi and infected into Festuca arundinacea by Agrobacterium-mediated method. The expression of FaCO gene was regulated by photoperiod. The over-expression of FaCO promoted flowering in wild type of Arabidopsis thaliana under long day condition and rescued the late flowering phenotype in co-2 mutant of Arabidopsis thaliana. Silencing FaCO gene in Festuca arundinacea by RNAi showed late-flowering phenotype or always kept in the vegetative growth stage. Our understanding the function of FaCO in flowering regulation will help further understand biological function of this gene in Festuca arundinacea.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.13345/j.cjb.200465DOI Listing
April 2021

Sulfopin is a covalent inhibitor of Pin1 that blocks Myc-driven tumors in vivo.

Nat Chem Biol 2021 May 10. Epub 2021 May 10.

Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.

The peptidyl-prolyl isomerase, Pin1, is exploited in cancer to activate oncogenes and inactivate tumor suppressors. However, despite considerable efforts, Pin1 has remained an elusive drug target. Here, we screened an electrophilic fragment library to identify covalent inhibitors targeting Pin1's active site Cys113, leading to the development of Sulfopin, a nanomolar Pin1 inhibitor. Sulfopin is highly selective, as validated by two independent chemoproteomics methods, achieves potent cellular and in vivo target engagement and phenocopies Pin1 genetic knockout. Pin1 inhibition had only a modest effect on cancer cell line viability. Nevertheless, Sulfopin induced downregulation of c-Myc target genes, reduced tumor progression and conferred survival benefit in murine and zebrafish models of MYCN-driven neuroblastoma, and in a murine model of pancreatic cancer. Our results demonstrate that Sulfopin is a chemical probe suitable for assessment of Pin1-dependent pharmacology in cells and in vivo, and that Pin1 warrants further investigation as a potential cancer drug target.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41589-021-00786-7DOI Listing
May 2021

Analysis of the relationship between geography and body color with the genetic diversity in the Echiura worm based on the mitochondrial and D-loop sequences.

Mitochondrial DNA B Resour 2021 Apr 15;6(4):1380-1386. Epub 2021 Apr 15.

Dalian Modern Agricultural Production Development Service Center, Dalian Aquatic Technology Promotion Station, Dalian, China.

is the only species distributed in Bohai Gulf of China. The wild populations of this species have sharply declined in China due to overfishing. Over 150 samples from Bohai Gulf were collected in the present study, which were classified into five populations according to their geographic areas and body colors. The genetic diversity and population structure of these populations were investigated by mitochondiral and D-loop sequences. The haplotype diversity of based on and D-loop sequences were still high. In addition, the evolution rate of D-loop region could faster than the gene of . Meanwhile, over 99% genetic diversity was contributed by different individuals within populations. Moreover, phylogenetic trees did not show clear geographic or color cluster. Our findings indicated that this species in Bohai Gulf of China should be treated as a whole population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/23802359.2021.1910082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078999PMC
April 2021

Multiplex PCR method for simultaneous detection of five pathogenic bacteria closely related to foodborne diseases.

3 Biotech 2021 May 16;11(5):219. Epub 2021 Apr 16.

School of Medical Technology, Xuzhou Medical University, No. 209 Tongshan Road, Yunlong District, Xuzhou, 221004 China.

In this study, we describe a multiplex PCR method for the detection of five food-relevant virulence pathogenicity genes of intestinal pathogens. Five pairs of primers were designed based on gene for , gene of , gene of , gene of and gene of . Conditions were optimized to amplify fragments of those genes simultaneously in one PCR amplification. After developing and optimizing the multiplex PCR reaction system, the specificity and sensitivity of the multiple PCR assays were evaluated. The optimized program is also applied to retail meat for testing. The result indicated that when the annealing temperature was 54 °C and the primer concentrations of and are 10, 10, 5, 3 and 2 μM, the five strains could expand 484, 345, 204, 156, 88 bp of clear fragments, respectively. So was the multiple PCR in artificially contaminated beef produce. All cultures were cultured and separated by traditional methods. The multiplex PCR method offers a rapid, simple, and accurate identification of pathogens and could be used in food safety investigations, clinical diagnosis as well as for the surveillance of the spreading determinants of pathogens in epidemiological studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13205-021-02759-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052391PMC
May 2021

Psychometric Properties of Flourishing Scales From a Comprehensive Well-Being Assessment.

Front Psychol 2021 21;12:652209. Epub 2021 Apr 21.

Sustainability and Health Initiative (SHINE), Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, United States.

In this article, we develop a measure of complete well-being. The framework is derived from the theoretical model of human flourishing understood as a state in which all aspects of a human life are favorable. The approach extends beyond psychological well-being and reflects the World Health Organization definition of health that not only considers the health of body and mind but also embraces the wholeness of the person. The Well-Being Assessment (WBA) is a comprehensive instrument designed to assess holistic well-being in six domains: emotional health, physical health, meaning and purpose, character strengths, social connectedness, and financial security. Although each of these domains is distinct, all of them are nearly universally desired, and all but financial security constitute ends in themselves. Data were collected from a representative sample of working adults. A sample of 276 employees participated in the pilot, 2,370 participated in the first wave and 1,209 in the second wave of the survey. The WBA showed a good fitting (40 items, six factors), satisfactory reliability, test-retest correlation, and convergent/discriminant validity in relation to stability over time and relevant health measures, as well as a good fit to the data that were invariant over time, gender, age, education, and marital status. The instrument can be of use for scientists, practitioners, clinicians, public health officials, and patients. Adoption of more holistic measures of well-being that go beyond psychological well-being may help to shift the focus from health deficiencies to health and well-being promotion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyg.2021.652209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097094PMC
April 2021

Study of the collagen type VI alpha 3 (COL6A3) gene in Parkinson's disease.

BMC Neurol 2021 May 8;21(1):187. Epub 2021 May 8.

Department of Neurology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310009, People's Republic of China.

Background: To date, the genetic contribution to Parkinson's disease (PD) remains unclear. Mutations in the collagen type VI alpha 3 (COL6A3) gene were recently identified as a cause of isolated dystonia. Since PD and dystonia are closely related disorders with shared clinical and genetic characteristics, we explored the association between COL6A3 and PD in a Chinese cohort.

Methods: We performed genetic screening of COL6A3 in a Chinese cohort of 173 patients with sporadic PD and 200 healthy controls. We identified variants that are likely to have pathogenic effects based on: 1) a minor allele frequency of < 0.01; and 2) the variant being recognized as deleterious by at least 15 different in silico predicting tools. Finally, we tested the aggregate burden of COL6A3 on PD via SKAT-O analysis.

Results: First, we found compound heterozygous COL6A3 gene mutations in one early-onset PD patients. Then, we explored whether COL6A3 variants contributed to increased risk of developing PD in a Chinese population. We detected 21 rare non-synonymous variants. Pathogenicity predictions identified 7 novel non-synonymous variants as likely to be pathogenic. SKAT-O analysis further revealed that an aggregate burden of variants in COL6A3 contributes to PD (p = 0.038).

Conclusion: An increased aggregate burden of the COL6A3 gene was detected in patients with PD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12883-021-02215-7DOI Listing
May 2021

Nuclear Translocation of OsMFT1 That is Impeded by OsFTIP1 Promotes Drought Tolerance in Rice.

Mol Plant 2021 May 4. Epub 2021 May 4.

State Key Laboratory of Rice Biology, Zhejiang Provincial Key Laboratory of Crop Genetic Resources, Institute of Crop Science, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou, 310058, China. Electronic address:

Drought has been the leading environmental threat affecting the productivity of crops, and plants have evolved a series of mechanisms to adapt to drought stress. The FT-INTERACTING PROTEINs (FTIPs) and phosphatidylethanolamine-binding proteins (PEBPs) play key roles in developmental processes, whereas their roles in the regulation of stress response are still largely unknown. Here, we report that OsFTIP1 negatively affects drought response. Further study reveals that OsFTIP1 interacts with a PEBP, rice MOTHER OF FT AND TFL1 (OsMFT1), which promotes rice tolerance to drought treatment. OsMFT1 was found to interact with two key drought-related transcription factors, OsbZIP66 and OsMYB26, and regulates their binding capacity on drought-related genes, thus enhancing drought tolerance in rice. We further revealed that OsFTIP1 impedes the nucleocytoplasmic translocation of OsMFT1. These results demonstrate that dynamic modulation of drought responsive genes by OsMFT1-OsMYB26 complex and OsMFT1-OsbZIP66 complex is integral to OsFTIP1 effect on impeding nuclear translocation of OsMFT1. Our findings suggest that OsMFT1 acts as a hitherto unknown nucleocytoplasmic trafficking signal that regulates drought tolerance in rice in response to environmental signals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.molp.2021.05.001DOI Listing
May 2021

Patient-specific iPSC-derived cardiomyocytes reveal abnormal regulation of FGF16 in a familial atrial septal defect.

Cardiovasc Res 2021 May 6. Epub 2021 May 6.

Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Medical College, Soochow University, Suzhou, 215000, China.

Aims: Congenital heart disease (CHD) frequently occurs in newborns due to abnormal formation of the heart or major blood vessels. Mutations in the GATA4 gene, which encodes GATA binding protein 4, are responsible for atrial septal defect (ASD), a common CHD. This study aims to gain insights into the molecular mechanisms of CHD using human induced pluripotent stem cells (iPSCs) from a family cohort with ASD.

Methods And Results: Patient-specific iPSCs possess the same genetic information as the donor and can differentiate into various cell types from all three germ layers in vitro, thus presenting a promising approach for disease modeling and molecular mechanism research. Here, we generated a patient-specific iPSC line (iPSC-G4T280M) from a family cohort carrying a hereditary ASD mutation in GATA4 gene (T280M), as well as a human embryonic stem cell line (ESC-G4T280M) carrying the isogenic T280M mutation using the CRISPR/Cas9 genome editing method. The GATA4-mutant iPSCs and ESCs were then differentiated into cardiomyocytes (CMs) to model GATA4 mutation-associated ASD. We observed an obvious defect in cell proliferation in cardiomyocytes derived from both GATA4T280M-mutant iPSCs (iPSC-G4T280M-CMs) and ESCs (ESC-G4T280M-CMs), while the impaired proliferation ability of iPSC-G4T280M-CMs could be restored by gene correction. Integrated analysis of RNA-Seq and ChIP-Seq data indicated that FGF16 is a direct target of wild-type GATA4. However, the T280M mutation obstructed GATA4 occupancy at the FGF16 promoter region, leading to impaired activation of FGF16 transcription. Overexpression of FGF16 in GATA4-mutant cardiomyocytes rescued the cell proliferation defect. The direct relationship between GATA4T280M and ASD was demonstrated in a human iPSC model for the first time.

Conclusions: In summary, our study revealed the molecular mechanism of the GATA4T280M mutation in ASD. Understanding the roles of the GATA4-FGF16 axis in iPSC-CMs will shed light on heart development and provide novel insights for the treatment of ASD and other CHD disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cvr/cvab154DOI Listing
May 2021

MDM2 induces EMT via the B‑Raf signaling pathway through 14‑3‑3.

Oncol Rep 2021 Jul 6;46(1). Epub 2021 May 6.

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, P.R. China.

MDM2 proto‑oncogene, E3 ubiquitin protein ligase (MDM2) is a well‑known oncogene and has been reported to be closely associated with epithelial‑to‑mesenchymal transition (EMT). The present study first demonstrated that the expression levels of MDM2 were markedly increased in TGF‑β‑induced EMT using quantitative PCR and western blotting. In addition, MDM2 was demonstrated to be associated with pathological grade in clinical glioma samples by immunohistochemical staining. Furthermore, overexpression of MDM2 promoted EMT in glioma, lung cancer and breast cancer cell lines using a scratch wound migration assay. Subsequently, the present study explored the mechanism by which MDM2 promoted EMT and revealed that MDM2 induced EMT by upregulating EMT‑related transcription factors via activation of the B‑Raf signaling pathway through tyrosine 3‑monooxygenase activation protein ε using RNA sequencing and western blotting. This mechanism depended on the p53 gene. Furthermore, experiments and the colony formation experiment demonstrated that MDM2 could promote tumor progression and induce EMT via the B‑Raf signaling pathway. Since EMT contributes to increased drug resistance in tumor cells, the present study also explored the relationship between MDM2 and drug sensitivity using an MTT assay, and identified that MDM2 promoted cell insensitivity to silibinin treatment in an EMT‑dependent manner. This finding is crucial for the development of cancer therapies and can also provide novel research avenues for future biological and clinical studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/or.2021.8071DOI Listing
July 2021

Computer-assisted mandibular curved osteotomy: An automatic method to design the new aesthetic gonion and osteotomy line.

J Plast Reconstr Aesthet Surg 2021 Apr 6. Epub 2021 Apr 6.

Department of Craniomaxillofacial Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.33 Badachu Road, Shijingshan District, Beijing 100144, People's Republic of China. Electronic address:

Background: Digital technology has been widely used in mandibular curved osteotomy to improve accuracy. However, the planning process still highly dependent on the experience and judgement of the surgeon. This study describes an automatic method to design the new gonion and osteotomy line based on the aesthetic standards in attractive women, and assesses its clinical outcomes.

Methods: An automatic surgical planning method for mandibular curved osteotomy was developed based on our previous research of mandibular angle aesthetics. A prospective clinical study was conducted from April 2016 to April 2018. Twenty-five female patients with prominent mandibular angle were enrolled. Pre- and postoperative skull computed tomography (CT) was performed. Three-dimensional (3D) CT data were obtained and processed by Mimics 18.0. Surgical templates were designed according to the automatic surgical planning method and 3D printed for the surgery. Preoperative measurements, surgical simulation and postoperative measurements were taken to evaluate the surgical outcomes.

Results: There were significant differences between the preoperative and the postoperative groups' results (p < 0.01). There was no difference between the surgical simulation and the postoperative results. All postoperative measurements were consistent with aesthetic features of mandibles. Patients were satisfied with their outcomes in terms of outline, symmetry and lower facial width.

Conclusions: Our study developed an automatic method to position the new aesthetic gonion and osteotomy line for prominent mandibular angle patients. We proved that this method is safe, effective and reliable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bjps.2021.03.067DOI Listing
April 2021

Cross-Sectional Study of the Effects of Job Burnout on Immune Function in 105 Female Oncology Nurses at a Tertiary Oncology Hospital.

Med Sci Monit 2021 May 4;27:e929711. Epub 2021 May 4.

Nursing Department, Guangxi Medical University Affiliated Cancer Hospital, Nanning, Guangxi, China (mainland).

BACKGROUND Nurses who work in hospitals experience a high level of burnout and the relationship between immune variables and burnout syndrome has yet to be elucidated. The aim of the present study was to investigate the effects of job burnout on immune function in female oncology nurses in a tertiary oncology hospital in Guangxi, China. The aspects of the human immune system evaluated were humoral and cellular immunity and complement components 3 (C3) and 4 (C4). MATERIAL AND METHODS We administered the Maslach Burnout Inventory-General Survey (MBI-GS), which includes scales for emotional exhaustion, depersonalization (DP), and personal accomplishment (PA), to measure variables related to immune function in 105 female nurses in a tertiary oncology hospital in Guangxi, China. Levels of humoral immunity and C3 and C4 were detected with immune turbidimetry. Cellular immunity was assessed with indirect immunofluorescence. RESULTS A Spearman rank correlation analysis revealed that levels of C3, C4, and CD4- and CD8-positive T cells were significantly associated with burnout symptoms (P<0.05, P<0.01, and P<0.05, respectively). Furthermore, there was a correlation between demographic data and humoral and cellular immunity (both P<0.05). Multivariable linear regression analysis showed that C4 levels were closely related to DP (P<0.05) and that CD4 and CD8 levels were closely related to PA (P<0.01). CONCLUSIONS These results suggest that DP and PA have an impact on immune function, and that timely psychological and behavioral interventions can be used to reduce the degree of job burnout among nurses and regulate their immunity, thus enabling them to better serve patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12659/MSM.929711DOI Listing
May 2021

A Randomized, Double-Blind, and Placebo-Controlled Trial of Chinese Herbal Medicine in the Treatment of Childhood Constipation.

Clin Transl Gastroenterol 2021 May 3;12(5):e00345. Epub 2021 May 3.

Departments of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, P.R. China.

Objectives: Management of constipation is still challenging in childhood. The pharmacological effect of XiaojiDaozhi Decoction, a prescription of Chinese Herbal Medicine (CHM), has been well described for the treatment of food and Qi stagnation which account for childhood constipation. However, the efficacy and safety of XiaojiDaozhi Decoction in childhood constipation remains unclear.

Methods: A randomized, double-blind, and placebo-controlled trial was conducted to evaluate the efficacy and safety of XiaojiDaozhi Decoction in childhood constipation. Two hundred children were recruited and randomly allocated to the CHM or placebo group to receive their respective interventions. The duration of treatment was 8 weeks, with a 12-week follow-up. Main outcome measures were complete spontaneous bowel movements and satisfaction with bowel function. Safety and adverse effects were evaluated by blood laboratory measurements.

Results: At the end of follow-up, the response rates of CHM and placebo were 62% and 31%, respectively (χ2 = 19.315, P < 0.01). At the end of treatment, recurrence was found in 7 cases (10.14%) in CHM and 11 cases (26.19%) in placebo (χ2 = 4.947, P < 0.05). In the main outcome measures, 56 patients (56%) in the CHM group and 25 patients (25%) in the placebo group were satisfied with their bowel movements (χ2 = 19.940, P < 0.05). Increased complete spontaneous bowel movements ≥3 per week from baseline were found in 40 patients (40%) who received CHM and 19 patients (19%) who received placebo (χ2 = 10.602, P < 0.05). No serious adverse effects were found in any of the recruited cases.

Discussion: CHM XiaojiDaozhi Decoction is a safe and effective method for the treatment of childhood constipation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14309/ctg.0000000000000345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096462PMC
May 2021

Activation of the Melanocortin-4 receptor signaling by α-MSH stimulates nerve-dependent mouse digit regeneration.

Cell Regen 2021 May 3;10(1):19. Epub 2021 May 3.

Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China.

Background: Expression of Mc4r in peripheral organs indicates it has broader roles in organ homeostasis and regeneration. However, the expression and function of Mc4r in the mouse limb and digit has not been fully investigated. Our previous work showed that Mc4r-/- mice fail to regenerate the digit, but whether activation of MC4R signaling could rescue digit regeneration, or stimulate proximal digit regeneration is not clear.

Results: We analyzed the expression dynamics of Mc4r in the embryonic and postnatal mouse limb and digit using the Mc4r-gfp mice. We found that Mc4r-GFP is mainly expressed in the limb nerves, and in the limb muscles that are undergoing secondary myogenesis. Expression of Mc4r-GFP in the adult mouse digit is restricted to the nail matrix. We also examined the effect of α-MSH on mouse digit regeneration. We found that administration of α-MSH in the Mc4r+/- mice rescue the delayed regeneration of distal digit tip. α-MSH could rescue distal digit regeneration in denervated hindlimbs. In addition, α-MSH could stimulate regeneration of the proximally amputated digit, which is non-regenerative.

Conclusions: Mc4r expression in the mouse limb and digit is closely related to nerve tissues, and α-MSH/MC4R signaling has a neurotrophic role in mouse digit tip regeneration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13619-021-00081-9DOI Listing
May 2021

Complex Coronary Instent Chronic Total Occlusion Lesions: Oxidative Stress, Inflammation, and Coronary Stent Lengths.

Oxid Med Cell Longev 2021 15;2021:8815048. Epub 2021 Apr 15.

Department of Geriatrics, The Affiliated Huaian Hospital of Xuzhou Medical University, Huaian 223002, China.

The oxidative stress and inflammation played the key roles in the development of atherosclerotic coronary plaques. However, the relationships between pro/antioxidant, pro/anti-inflammatory status, and complex coronary instent chronic total occlusion lesions were not clear in the elderly patients with very long stent implantations. We tried to evaluate the roles of pro/antioxidant and pro/anti-inflammatory biomarkers in the diagnosis of complex reocclusion lesions in elderly patients after coronary stenting. We evaluated the expression levels of acrolein (ACR), malondialdehyde (MDA), high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor- (TNF-), superoxide dismutase 3 (SOD3), paraoxonase-1 (PON-1), endothelial nitric oxide synthase (eNOS), and stromal cell-derived factor-1 (SDF-1) in the elderly patients with very long stent implantations and complex reocclusion lesions. Levels of ACR, MDA, hs-CRP, and TNF- were remarkably increased ( < 0.001), and levels of SOD3, PON-1, eNOS, and SDF-1 were decreased significantly ( < 0.001) in the elderly patients with very long stents and complex reocclusion lesions. The prooxidant and proinflammatory biomarkers were remarkably increased, as well as antioxidant and anti-inflammatory biomarkers were decreased significantly in the elderly patients with very long stent implantations and complex reocclusion lesions after coronary stenting. In conclusion, these findings indicated that the imbalance between prooxidant/proinflammatory and antioxidant/anti-inflammatory status was associated with complex reocclusion lesions, suggesting that oxidative stress and inflammation played the key roles in progression of complex reocclusion lesions in the elderly patients with very long stent implantations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/8815048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062172PMC
April 2021

PHLDA3 inhibition attenuates endoplasmic reticulum stress-induced apoptosis in myocardial hypoxia/reoxygenation injury by activating the PI3K/AKT signaling pathway.

Exp Ther Med 2021 Jun 14;21(6):613. Epub 2021 Apr 14.

Department of General Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570311, P.R. China.

Endoplasmic reticulum stress (ERS)-induced apoptosis serves a crucial role in the pathogenesis of myocardial ischemia/reperfusion injury (MIRI). Previous studies have confirmed that pleckstrin homology-like domain family A member 3 (PHLDA3) is an important mediator in ERS-associated apoptosis. The aim of the current study focused on whether PHLDA3 served protective effects on hypoxia/reoxygenation (H/R)-injured cardiomyocytes by inhibiting ERS-induced apoptosis. Furthermore, the molecular mechanisms associated with the PI3K/AKT signaling pathway were investigated. Primary neonatal rat cardiomyocytes were isolated and randomized into four groups: i) Control + adenovirus encoding scrambled short hairpin RNA (AdshRNA); ii) control + adenoviral vectors encoding PHLDA3 shRNA (AdshPHLDA3); iii) H/R+ AdshRNA and iv) H/R+AdshPHLDA3. AdshPHLDA3 was used to knock down PHLDA3. An H/R injury model was constructed by treatment with hypoxia for 4 h followed by reoxygenation for 6 h. A PI3K/AKT inhibitor, LY294002, was supplemented in mechanistic studies. Cell viability and LDH/CK releases were detected to evaluate myocardial damage. Flow cytometry assays were used to assess apoptotic response. Western blotting assays were used to detect protein expression. The results demonstrated that H/R induced myocardial damage and increased PHLDA3 expression. ERS-induced apoptosis was significantly increased following H/R injury, as indicated by increased apoptotic rates and ERS-associated protein expression, including those of CHOP, 78 kDa glucose-regulated protein and caspase-12. However, PHLDA3 inhibition following AdshPHLDA3 transfection reversed cell damage and ERS-associated apoptosis on H/R injury. Studies for molecular mechanisms concluded that the apoptosis-inhibition effects and cardioprotective roles of PHLDA3 inhibition were induced partly by the activation of the PI3K/AKT pathway, which was verified by LY294002 treatment. In conclusion, in the process of H/R injury, PHLDA3 inhibition reduced ERS-induced apoptosis and H/R injury by activating the PI3K/AKT pathway. PHLDA3 may be a therapeutic target for the treatment of MIRI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2021.10045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082641PMC
June 2021

[Involvement of Pirt /TRPV1 signaling in acupuncture-induced reduction of visceral hypersensitivity in diarrhea-predominant irritable bowel syndrome rats].

Zhen Ci Yan Jiu 2021 Apr;46(4):278-83

School of Acupuncture-moxibustion and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China.

Objective: To observe the effect of electroacupuncture (EA) on the expression of Pirt (a regulator of TRPV1) in the dorsal root ganglia (DRG) and transient receptor potential vanilloid 1 (TRPV1, a molecular sensor of noxious heat and capsaicin) in the colonic mucosa in rats suffering from diarrhea-predominant irritable bowel syndrome (IBS-D), so as to explore its mechanisms underlying alleviation of visceral hypersensitivity of IBS-D.

Methods: Forty SD rats (half male and half female) were randomly assigned to control, model, EA, and medication groups by lottery, with 10 rats in each group. The IBS-D model was established by chronic unpredictable mild stress (CUMS) and gavage of senna soaking fluid. Rats in the EA group received EA (2 Hz/15 Hz,0.1-1 mA) stimulation of unilateral "Tianshu"(ST25), "Zusanli" (ST36), "Sanyinjiao"(SP6) and "Taichong"(LR3) for 15 min once a day for 14 days, and rats of the medication group received intragastric administration of pinave-rium bromide (10 mL/kg, 2.7 mg/mL) once daily for 14 days. The visceral pain threshold (VPT) was measured by using abdominal wall withdrawal reflex (AWR) test. The diarrhea index (loose stool rate [total number of loose stool/total number of defecation] X mean loose degree [0-4 grades according to the filter paper stain diameter] in 6 h/d) was used to assess the severity of diarrhea. The expression of Pirt in the DRG and TRPV1 in the colonic mucosa tissue was detected using immunohistochemistry.

Results: After modeling, the VPT was obviously reduced (<0.01), while the diarrhea index, mean optical density of Pirt and TRPV1 were remarkably increased in the model group relevant to the control group (<0.01). After the interventions, the VPT was obviously increased while the diarrhea index, and the mean optical density of Pirt and TRPV1 was noticeably decreased in both EA and the medicine groups in contrast to the model group (<0.01). No significant differences were found between the EA and medicine groups in up-regulating VPT and down-regulating the diarrhea index, and Pirt and TRPV1 expression (>0.05).

Conclusion: EA can effectively alleviate visceral hypersensitivity in IBS-D rats, which may be related to its effect in down-regulating the expression level of DRG Pirt and colonic TRPV1.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.13702/j.1000-0607.200442DOI Listing
April 2021

Da Cheng Qi Decoction Alleviates Cerulein-Stimulated AR42J Pancreatic Acinar Cell Injury via the JAK2/STAT3 Signaling Pathway.

Evid Based Complement Alternat Med 2021 9;2021:6657036. Epub 2021 Apr 9.

Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Background: Acute pancreatitis (AP) is a common acute abdomen inflammation, characterized by the dysregulation of digestive enzyme production and secretion. Many studies have shown that Da Cheng Qi Decoction (DCQD) is a secure, effective prescription on AP. In this study, cerulein-stimulated AR42J cells damage model was established to further explore the feasibility and underlying mechanism of DCQD as a potential inhibitor of JAK2/STAT3 pathway for the treatment of AP.

Methods: Cell viability of DCQD was measured using a cell counting Kit-8 assay. Pancreatic biochemical markers such as amylase, lipase, and C-reactive protein production were measured by assay kits, respectively. Cytokines (TNF-, IL-6, IL-10, and IL-1) were assayed by ELISA. Protein location and protein expression were detected by immunofluorescence staining and Western blotting, respectively. Gene expression was assessed by real-time PCR. For mechanistic analysis of the effect of DCQD on JAK2/STAT3 signaling pathway, selective JAK2 inhibitor (Fedratinib) and STAT3 inhibitor (Stattic) as well as STAT3 activator (Garcinone D) were used.

Results: DCQD protected cells by regulating cerulein-induced inflammation and reducing the secretion of pancreatic biochemical markers. Moreover, DCQD could not only inhibit the nuclear translocation of p-STAT3, but also decrease the mRNA expression of JAK2 and STAT3 as well as the ratio of p-JAK2/JAK2 and p-STAT3/STAT3 in protein level. Additionally, DCQD could regulate the mRNA and protein expression of JAK2/STAT3 downstream effectors, Bax and Bcl-XL. The activated effect of cerulein on JAK2/STAT3 pathway was also reversed by JAK2 inhibitor Fedratinib or STAT3 inhibitor Stattic. And the overexpression of JAK2/STAT3 pathway, via STAT3 activator Garcinone D, did exert damage on cells, which bore a resemblance to cerulein.

Conclusion: The activation of JAK2/STAT3 pathway may play a key role in the pathogenesis of cerulein-stimulated AR42J pancreatic acinar cell injury. DCQD could improve inflammatory cytokines and cell injury, which might be mediated by suppressing the activation of JAK2/STAT3 signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/6657036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053057PMC
April 2021

Deaths from COPD in patients with cancer: a population-based study.

Aging (Albany NY) 2021 Apr 27;13. Epub 2021 Apr 27.

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

Features of the deaths caused by COPD (chronic obstructive pulmonary disease) in cancer patients remained a controversial issue. This study aimed to characterize the demographic characteristics and mortality rates of the deaths from COPD in patients with cancer. In total, 7,846,370 cancer patients aged 40 years or older in the United States were identified from the Surveillance, Epidemiology, and End Results database (1975-2016). Mortality rates and SMRs (standardized mortality ratios) adjusted by age, race, sex, and calendar year were calculated to investigate the risk of COPD deaths in cancer survivors and to compare it with the general population. A total of 119,228 COPD deaths in patients with cancer were recorded, with a mortality rate of 261.5/100,000 person-years, nearly two-fold that of the general population (SMR, 2.17; 95% CI [confidence interval], 2.16-2.18). The proportion of cancer survivors dying from COPD increased from 0.9% in 1975 to 3.4% in 2016. Patients with lung cancer had a higher overall risk (SMR, 9.23; 95% CI, 9.12-9.35) than those with extrapulmonary malignancies. Among all extrapulmonary sites, laryngeal (SMR, 5.54; 95% CI, 5.34-5.75) and esophageal cancers (SMR, 4.33; 95% CI, 4.04-4.63) had the highest SMR. The risk of death from COPD increased with follow-up time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.202939DOI Listing
April 2021

Biodegradable Flexible Electronic Device with Controlled Drug Release for Cancer Treatment.

ACS Appl Mater Interfaces 2021 Apr 28. Epub 2021 Apr 28.

AML, Department of Engineering Mechanics, Tsinghua University, Beijing 100084, China.

Nowadays, controllable drug release is a vitally important strategy for cancer treatment and usually realized using implanting biocompatible devices. However, these devices need to be removed by another surgery after the function fails, which brings the risks of inflammation or potential death. In this article, a biodegradable flexible electronic device with controllable drug (paclitaxel) release was proposed for cancer treatment. The device is powered by an external alternating magnetic field to generate internal resistance heat and promote drug release loaded on the substrate. Moreover, the device temperature can even reach to 65 °C, which was sufficient for controllable drug release. This device also has similar mechanical properties to human tissues and can autonomously degrade due to the structure design of the circuit and degradable compositions. Finally, it is confirmed that the device has a good inhibitory effect on the proliferation of breast cancer cells (MCF-7) and could be completely degraded . Thus, its great biodegradability and conformity can relieve patients of second operation, and the device proposed in this paper provides a promising solution to complete conquest of cancer .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.1c04653DOI Listing
April 2021

Transmission dynamics of the rubella virus circulating in China during 2010-2019: two lineage switches between genotypes 1E and 2B.

Clin Infect Dis 2021 Apr 27. Epub 2021 Apr 27.

Yunnan Provincial Center for Disease Control and Prevention, Kunming, China.

Background: To provide a better understanding of the progress on rubella control and elimination in China, a genetic analysis was conducted to examine the transmission pattern of the endemic rubella virus in China during 2010-2019.

Methods: Total 4895 strains were obtained from 29 out of the 31 provinces in mainland of China during 2010-2019. The genotyping region of the strains were amplified, determined, and assembled. Genotyping analysis and lineage division were performed by comparisons with the World Health Organization reference strains and previously reported lineage reference strains, respectively. Further phylogenetic analyses were performed to compare the genetic relationship.

Results: During 2010-2019, the domestic lineage 1E-L1 and multiple imported lineages of rubella viruses including 2B-L1, 1E-L2, and 2B-L2c were identified. Further analysis of the circulation trend of the different lineages indicated that two switches occurred among the lineages. The first shift was from lineage 1E-L1 to 2B-L1, which occurred around 2015-2016, followed by the lowest rubella incidence in 2017. The second shift was from lineage 2B-L1 to 1E-L2 and 2B-L2c, which occurred around 2018-2019, coinciding with rubella resurgence and the subsequent nationwide epidemic during 2018-2019. Insufficient genomic information worldwide made it impossible to trace the origin of the imported viruses in this study.

Conclusions: China was moving toward rubella elimination, as evidenced by the fact that previous endemic lineages were not detected. However, rubella reemerged in 2018 and 2019 due to the newly imported rubella viruses. Therefore, to realize the rubella elimination goal, joint efforts are required for all countries worldwide.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciab339DOI Listing
April 2021

Rs2686344 and serum squamous cell carcinoma antigen could predict clinical efficacy of neoadjuvant chemotherapy for cervical cancer.

Curr Probl Cancer 2021 Apr 18:100755. Epub 2021 Apr 18.

Department of Gynecology & Obstetrics, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China. Electronic address:

Objective: To evaluate the predictive value of a single nucleotide polymorphism (SNP) rs2686344 and squamous cell carcinoma antigen (SCCAg) levels in the clinical efficacy of neoadjuvant chemotherapy (NACT) for cervical cancer.

Methods: A total of 92 patients with stage IB2-IIIB carcinoma of the uterine cervix who received NACT treatment were enrolled. The relationship between the genotypes of SNP rs2686344 which is located on CAMKK2 on chromosome 12, SCCAg levels and the response to NACT was analyzed. The relationship between the SNP rs2686344 genotypes, SCCAg levels, the response to NACT and the five-year survival rate was evaluated.

Results: The effective group accounted for 84.85% in patients with low level (≤3.5 ng/mL) of post-treatment SCCAg (post-SCCAg), while the ineffective group accounted for 15.15%. The post-SCCAg levels and the genotypes of rs2686344 were significantly correlated with NACT response (P = 0.003, and P = 0.006). In patients with CC or CT genotype of SNP rs2686344, effective group accounted for 81.18%, while ineffective group accounted for 18.82%; For patients with TT genotype, effective response group accounted for 28.57%, ineffective group accounted for 71.43%. Post-SCCAg level >3.5 ng/mL and TT genotype of SNP rs2686344 showed as independent risk factors for NACT response in the multivariate analysis (P = 0.002, and P = 0.048). There was no significant difference in 5-year overall survival and 5-year disease-free survival between patients with different levels of post-SCCAg, or among different rs2686344 genotypes.

Conclusion: The high level of post-SCCAg (>3.5 ng/mL) and TT genotype of rs2686344 may suggest a higher risk of poor response to NACT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.currproblcancer.2021.100755DOI Listing
April 2021

Degradation of the photosystem II core complex is independent of chlorophyll degradation mediated by Stay-Green Mg dechelatase in Arabidopsis.

Plant Sci 2021 Jun 3;307:110902. Epub 2021 Apr 3.

Institute of Low Temperature Science, Hokkaido University, Sapporo, Japan. Electronic address:

During leaf senescence, the degradation of photosystems and photosynthetic pigments proceeds in a coordinated manner, which would minimize the potential photodamage to cells. Both photosystem I and II are composed of core complexes and peripheral antenna complexes, with the former binding chlorophyll a and the latter binding chlorophyll a and b. Although the degradation of peripheral antenna complexes is initiated by chlorophyll degradation, it remains unclear whether the degradation of core complexes and chlorophyll is coordinated. In this study, we examined the degradation of peripheral antenna and core complexes in the Arabidopsis sgr1/sgr2/sgrl triple mutant, lacking all the isoforms of chlorophyll a:Mg dechelatase. In this mutant, the degradation of peripheral antenna complexes and photosystem I core complexes was substantially retarded, but the core complexes of photosystem II were rapidly degraded during leaf senescence. On the contrary, the photosynthetic activity declined at a similar rate as in the wild type plants. These results suggest that the degradation of photosystem II core complexes is regulated independently of the major chlorophyll degradation pathway mediated by the dechelatase. The study should contribute to the understanding of the complex molecular mechanisms underlying the degradation of photosystems, which is an essential step during leaf senescence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.plantsci.2021.110902DOI Listing
June 2021

Comparative differences in musculoskeletal pain consultation and analgesic prescription for people with dementia: a UK-wide matched cohort study.

Pain 2021 Mar 9. Epub 2021 Mar 9.

School of Medicine, Keele University, Staffordshire, United Kingdom Department of Health and Environmental Sciences, Xi'an Jiaotong Liverpool University, Suzhou, China Midlands Partnership NHS Foundation Trust, St Georges' Hospital, Stafford, United Kingdom.

Abstract: Painful musculoskeletal conditions are common in older adults; however, pain identification, assessment, and management are reported to be suboptimal for people with dementia. Adequate pain management is an integral aspect of care for people with dementia to prevent or delay negative outcomes, such as behavioural and psychological changes, emergency department attendance, and premature nursing home admission. This study aims to examine musculoskeletal consultations and analgesic prescriptions for people with dementia compared with those for people without dementia. A dementia cohort (n = 36,582) and matched cohort were identified in the Clinical Practice Research Datalink (a UK-wide primary care database). Period prevalence for musculoskeletal consultations and analgesic prescriptions was described, and logistic regression applied to estimate associations between dementia and musculoskeletal consultation or analgesic prescription from the time of dementia diagnosis to 5 years after diagnosis. People with dementia had a consistently (over time) lower prevalence and odds of musculoskeletal consultation and analgesic prescription compared with people without dementia. The evidence suggests that pain management may be suboptimal for people with dementia. These results highlight the need to increase awareness of pain and use better methods of pain assessment, evaluation of treatment response, and acceptable and effective management for people with dementia, in primary care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/j.pain.0000000000002257DOI Listing
March 2021

Genetic Mutation of SARS-CoV-2 during Consecutive Passages in Permissive Cells.

Virol Sin 2021 Apr 26. Epub 2021 Apr 26.

CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12250-021-00384-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071843PMC
April 2021

Study the lipidoid nanoparticle mediated genome editing protein delivery using 3D intestinal tissue model.

Bioact Mater 2021 Nov 6;6(11):3671-3677. Epub 2021 Apr 6.

Department of Biomedical Engineering, Tufts University, Medford, MA, USA.

Lipid nanoparticles are promising carriers for oral drug delivery. For bioactive cargos with intracellular targets, e.g. gene-editing proteins, it is essential for the cargo and carrier to remain complexed after crossing the epithelial layer of intestine in order for the delivery system to transport the cargos inside targeted cells. However, limited studies have been conducted to verify the integrity of cargo/carrier nanocomplexes and their capability in facilitating cargo delivery intracellularly after the nanocomplex crossing the epithelial barrier. Herein, we used a traditional 2D transwell system and a recently developed 3D tissue engineered intestine model and demonstrated the synthetic lipid nanoparticle (carrier) and protein (cargo) nanocomplexes are able to cross the epithelial layer and deliver the protein cargo inside the underneath cells. We found that the EC16-63 LNP efficiently encapsulated the GFP-Cre recombinase, penetrated the intestinal monolayer cells in both the 2D cell culture and 3D tissue models through temporarily interrupting the tight junctions between epithelial layer. After transporting across the intestinal epithelia, the EC16-63 and GFP-Cre recombinase nanocomplexes can enter the underneath cells to induce gene recombination. These results suggest that the in vitro 3D intestinal tissue model is useful for identifying effective lipid nanoparticles for potential oral drug delivery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioactmat.2021.03.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056182PMC
November 2021

Identification and Characterization of Zika Virus NS5 Methyltransferase Inhibitors.

Front Cell Infect Microbiol 2021 7;11:665379. Epub 2021 Apr 7.

State Key Laboratory of Bioactive Substances and Function of Natural Medicine, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

The recurring outbreak of Zika virus (ZIKV) worldwide makes an emergent demand for novel, safe and efficacious anti-ZIKV agents. ZIKV non-structural protein 5 (NS5) methyltransferase (MTase), which is essential for viral replication, is regarded as a potential drug target. In our study, a luminescence-based methyltransferase assay was used to establish the ZIKV NS5 MTase inhibitor screening model. Through screening a natural product library, we found theaflavin, a polyphenol derived from tea, could inhibit ZIKV NS5 MTase activity with a 50% inhibitory concentration (IC) of 10.10 μM. Molecular docking and site-directed mutagenesis analyses identified D146 as the key amino acid in the interaction between ZIKV NS5 MTase and theaflavin. The SPR assay indicated that theaflavin had a stronger binding activity with ZIKV NS5 wild-type (WT)-MTase than it with D146A-MTase. Moreover, theaflavin exhibited a dose dependent inhibitory effect on ZIKV replication with a 50% effective concentration (EC) of 8.19 μM. All these results indicate that theaflavin is likely to be a promising lead compound against ZIKV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcimb.2021.665379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058401PMC
April 2021

Silencing of miR-150-5p Ameliorates Diabetic Nephropathy by Targeting SIRT1/p53/AMPK Pathway.

Front Physiol 2021 9;12:624989. Epub 2021 Apr 9.

Shanghai TCM-Integrated Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Diabetic nephropathy (DN) is a common complication of diabetes and an important cause of end-stage renal disease. Increasing evidence suggests that microRNAs (miRNAs) regulate the development of DN. In a preliminary study, high levels of miR-150-5p were detected in the serum and urine of patients with DN. Consequently, we investigated the effect and mechanism of action of miR-150-5p in DN and . Our results showed that inhibition of miR-150-5p reversed high glucose-induced podocyte injury and Streptozocin (STZ)-induced diabetic nephropathy in mice. Further analysis revealed that miR-150-5p targeted the 3' untranslated region (UTR) of sirtuin 1 (SIRT1), consequently decreasing SIRT1 levels in podocytes. Importantly, we found that the silencing of miR-150-5p promoted the interaction between SIRT1 and p53, causing the suppression of p53 acetylation in podocytes and kidney tissue. This resulted in the stimulation of AMP-activated protein kinase (AMPK)-dependent autophagy. In conclusion, our study demonstrated that the silencing of miR-150-5p played a reno-protective role in DN mice through targeting SIRT1.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2021.624989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064124PMC
April 2021

Selenium Deficiency Leads to Changes in Renal Fibrosis Marker Proteins and Wnt/β-Catenin Signaling Pathway Components.

Biol Trace Elem Res 2021 Apr 24. Epub 2021 Apr 24.

Department of Biochemistry and Molecular Biology, Harbin Medical University, Baojian Road 157, Nangang District, Harbin City, 150086, Heilongjiang, China.

Renal fibrosis is the final result of the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD). Earlier studies confirmed that selenium (Se) displays a close association with kidney diseases. However, the correlation between Se and fibrosis has rarely been explored. Thus, this article mainly aimed to investigate the effect of Se deficiency on renal fibrosis and the Wnt/β-catenin signaling pathway. Twenty BALB/c mice were fed a diet containing 0.02-mg/kg Se (Se-deficient diet) or 0.18-mg/kg Se (standard diet) for 20 weeks. A human glomerular mesangial cell (HMC) cell line was transfected with lentiviral TRNAU1AP-shRNA vector to establish a stable Se deficiency model in vitro. As indicated in this study, the glutathione (GSH) content in the Se-deficient group displayed an obvious decline compared with that in the control group, whereas the content of malondialdehyde (MDA) was obviously elevated. The results of Masson staining showed fibrosis around the renal tubules, and the results of immunohistochemistry showed that the area of positive fibronectin expression increased. In the Se-deficient group, the levels of collagen I, collagen III, matrix metalloproteinase 9 (MMP9), and other fibrosis-related proteins changed significantly in vivo and in vitro. Compared with the control group, the TRNAU1AP-shRNA group showed markedly reduced cell proliferation and migration abilities. Our data indicate that Se deficiency can cause kidney damage and renal fibrosis. Furthermore, the Wnt pathway is critical for the development of tissue and organ fibrosis. The data of this study demonstrated that the expression of Wnt5a, β-catenin, and dishevelled 1 (Dvl-1) was significantly upregulated in the Se-deficient group. Therefore, the Wnt/β-catenin pathway may play an important role in renal fibrosis caused by Se deficiency.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12011-021-02730-1DOI Listing
April 2021

Genetic interactions among Brca1, Brca2, Palb2, and Trp53 in mammary tumor development.

NPJ Breast Cancer 2021 Apr 23;7(1):45. Epub 2021 Apr 23.

Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.

Inherited mutations in BRCA1, BRCA2, and PALB2 cause a high risk of breast cancer. Here, we conducted parallel conditional knockout (CKO) of Brca1, Palb2, and Brca2, individually and in combination, along with one copy of Trp53, in the mammary gland of nulliparous female mice. We observed a functional equivalence of the three genes in their basic tumor-suppressive activity, a linear epistasis of Palb2 and Brca2, but complementary roles of Brca1 and Palb2 in mammary tumor suppression, as combined ablation of either Palb2 or Brca2 with Brca1 led to delayed tumor formation. Whole-exome sequencing (WES) revealed both similarities and differences between Brca1 and Palb2 or Brca2 null tumors. Analyses of mouse mammary glands and cultured human cells showed that combined loss of BRCA1 and PALB2 led to high levels of reactive oxygen species (ROS) and increased apoptosis, implicating oxidative stress in the delayed tumor development in Brca1;Palb2 double CKO mice. The functional complementarity between BRCA1 and PALB2/BRCA2 and the role of ROS in tumorigenesis require further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41523-021-00253-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065161PMC
April 2021