Publications by authors named "Yuanyuan Wu"

333 Publications

Effect of pH dynamic control on ethanol-lactic type fermentation (ELTF) performance of glucose.

Environ Technol 2021 Jun 17:1-37. Epub 2021 Jun 17.

State Key Joint Laboratory of Environment Simulation and Pollution Control, School of Environment, Tsinghua University, Beijing 100084, PR China.

This study proposed a new ethanol-lactic type fermentation (ELTF) and explored the optimal control strategy. Using batch experiments, the effects of pH, temperature and organic loading (OL) on ELTF was investigated. The sum of ethanol and lactic acid yield was highest at whole-control pH value of 4.0, 35℃ temperature and OL of 33 gCOD/L. To improve ELTF, the dynamic pH control in the long term CSTR was adjusted at 4.0 (1-28 day), 5.0 (29-44 day) and 4.0 (46-62 day) successively. The high concentration of ethanol and lactic acid was 8190.5 mg/L at 16 day of pH 4.0. At pH of 5.0, the average acidogenesis rate and total concentration of fermentation products increased 111.0% and 128.0%, respectively. Organisms of and were the predominant bacteria in reactor. It can achieve the directional regulation of ELTF and provides parameter support for the application of two-phase anaerobic digestion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09593330.2021.1942560DOI Listing
June 2021

ZEB1 induces non-small cell lung cancer development by targeting microRNA-320a to increase the expression of RAD51AP1.

Exp Cell Res 2021 Jun 4:112687. Epub 2021 Jun 4.

The First Department of Oncology, General Hospital of Ningxia Medical University, Yinchuan 750004, P.R. China. Electronic address:

Lung cancer is the most prevalent cancer worldwide, with its mortality rate reported to be in millions annually; one of the two subtypes is non-small cell lung cancer (NSCLC). In this study, we investigated the interactions and expressions of zinc finger E-box binding homeobox 1 (ZEB1), microRNA-320a (miR-320a) and RAD51-associated protein 1 (RAD51AP1) in NSCLC tissues to determine the roles of ZEB1 in regulation of miR-320a and RAD51AP1 in the development and metastasis of NSCLC. First, the expression levels of miR-320a and ZEB1 were quantified in NSCLC tissues and cells. Transfection assay was conducted to identify the effects of miR-320a on the progression of NSCLC cells. The interaction of miR-320a with ZEB1 and RAD51AP1 was predicted and verified using dual-luciferase reporter gene assay and chromatin immunoprecipitation assay. Finally, subcutaneous xenograft tumors of 6-week mice and metastatic model tumors of 8-week mice were established to further explore the in vivo effect of miR-320a/ZEB1/RAD51AP1 on NSCLC. The findings revealed a lower expression of miR-320a in NSCLC tissues and cells, while this result was reversed regarding ZEB1 expression. ZEB1 suppressed miR-320a expression and upregulation of miR-320a resulted in the reduction of proliferation, invasion and metastasis rate of NSCLC cells, and promoted NSCLC cell apoptosis. ZEB1 promoted the expression of RAD51AP1 via inhibition of miR-320a, promoting tumor growth in vivo. ZEB1 transcriptionally inhibited the expression of miR-320a and upregulated the expression of RAD51AP1, thereby promoting metastasis in NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yexcr.2021.112687DOI Listing
June 2021

Yap1-2 Isoform Is the Primary Mediator in TGF-β1 Induced EMT in Pancreatic Cancer.

Front Oncol 2021 19;11:649290. Epub 2021 May 19.

Institute of Life Sciences, Wenzhou University, Wenzhou, China.

Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive human malignancy and intrinsically resistant to conventional therapies. YAP1, as a key downstream effector of the Hippo pathway, plays an important role in tumorigenesis including PDAC. Alternative mRNA splicing of YAP1 results in at least 8 protein isoforms, which are divided into two subgroups (YAP1-1 and YAP1-2) based on the presence of either a single or double WW domains. We investigated the functions and regulatory mechanisms of YAP1-1 and YAP1-2 in PDAC cells induced by TGF-β to undergo epithelial-to-mesenchymal transition (EMT). CRISPR-Cas9 and shRNA were used to silence YAP1 expression in pancreatic cancer cells. Re-constituted lentivirus mediated overexpression of each single YAP1 isoform was generated in the parental knockout L3.6 cells. EMT was induced by treatment with TGF-β, EGF and bFGF in parental and the constructed stable cell lines. Western blot and qPCR were used to detect the expression of EMT markers. Scratch wound healing and transwell assays were used to detect cell migration. The stability and subcellular localization of YAP1 proteins were determined by Western blot analysis, immunofluorescence, as well as ubiquitination assays. We showed that TGF-β, EGF and bFGF all significantly promoted EMT in PDAC cells, which was inhibited by knockdown of YAP1 expression. Interestingly, YAP1-1 stable cells exhibited a stronger migratory ability than YAP1-2 cells under normal culture condition. However, upon TGF-β treatment, L3.6-YAP1-2 cells exhibited a stronger migratory ability than L3.6-YAP1-1 cells. Mechanistically, TGF-β treatment preferentially stabilizes YAP1-2 and enhances its nuclear localization. Furthermore, TGF-β-induced EMT and YAP1-2 activity were both blocked by inhibition of AKT signaling. Our results showed that both YAP1-1 and YAP1-2 isoforms are important mediators in the EMT process of pancreatic cancer. However, YAP1-2 is more important in mediating TGF-β-induced EMT, which requires AKT signaling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.649290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170464PMC
May 2021

Acetone Extract of Leaves Exerts Anti-Melanoma Effects via Inhibiting STAT3 Signaling.

Onco Targets Ther 2021 28;14:3487-3501. Epub 2021 May 28.

School of Pharmacy, Henan University of Traditional Chinese Medicine, Zhengzhou, People's Republic of China.

Purpose: This research aims to investigate the intervention and mechanism of 50% acetone extract of leaves (SZYY) on melanoma xenografts.

Patients And Methods: Tumor size and cardiac function were measured via ultrasound. The accumulation of 2-deoxy-D-glucose (2-DG) in tumor tissue was examined with near-infrared in vivo imaging. Flow cytometry was performed to assess apoptosis and reactive oxygen species (ROS) levels in tumor and immune cells in spleen. The levels of inflammatory cytokines in serum were detected by cytometric bead array. The expression of proliferation-, apoptosis-, and angiogenesis-related proteins in tumor cells was measured to evaluate the underlying mechanisms. Subsequently, the effects of four compounds separated from SZYY on the proliferation and migration of A375 cells and STAT3 signaling were examined. The peak identification and contents of the four components were performed via high-performance liquid chromatography (HPLC). Finally, we evaluated the inhibitory effects of STAT3 overexpression on the cytotoxic activity of four constituents in A375 cells.

Results: SZYY inhibited the growth and glycolysis of melanoma xenograft in mice, improved cardiac function, increased the percentages of macrophages, neutrophils, and lymphocytes in spleen, reduced the levels of IL-6, IL-17A, TNF-α, and IFN-γ in serum, promoted apoptosis and oxidative stress in tumor tissues, and inhibited STAT3 phosphorylation and expression of angiogenic factors. Chemical analysis showed that SZYY is rich in loganin, rutin, triohimas C, and triohimas D, which all could restrain the proliferation and migration of A375 cells and inhibit the phosphorylation and nuclear translocation of STAT3. Moreover, STAT3 overexpression could diminish the cytotoxic activity of four compounds on A375 cells.

Conclusion: SZYY could exert anti-melanoma effects via inhibiting STAT3 signaling to induce apoptosis and inhibit tumor angiogenesis. Its active ingredients might be loganin, rutin, triohimas C, and triohimas D.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/OTT.S308371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169088PMC
May 2021

Circulating Level of Monocyte Chemoattractant Protein-1 and Risk of Coronary Artery Disease: A Case-Control and Mendelian Randomization Study.

Pharmgenomics Pers Med 2021 11;14:553-559. Epub 2021 May 11.

Department of Cardiology, Jinan People's Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, 271100, People's Republic of China.

Background: Coronary artery disease (CAD) ranks the leading cause of death worldwide, and inflammation has been implicated in all stages of CAD and is considered to contribute to the pathophysiological basis of atherogenesis.

Methods: Here, we implemented a case-control study and a two-sample Mendelian randomization (MR) study to explore the associations between CAD risk and genetic predisposition to circulating level of monocyte chemoattractant protein-1 (MCP1), the most important regulator of monocyte trafficking.

Results: In case-control study, we found circulating level of MCP1 was significantly associated with increased risk of CAD (OR for per quartile increment: 1.33, 95% CI: 1.19-1.49, P<0.001). Further, genetically predicted higher level of MCP1 was significantly associated with higher risk of CAD (OR for 1-SD increase: 1.05, 95% CIs: 1.02-1.08, P value: 0.002) in MR analysis. Sensitivity analyses were also conducted to validate the main findings, and we also did not detect any directional pleiotropy effects using the MR Egger intercept test (P=0.831).

Conclusion: To sum up, our study suggested that increased CAD risk was associated with a predisposition to higher level of MCP1. Additional insight into the contribution of MCP1 to the occurrence of CAD is still needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/PGPM.S303362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124014PMC
May 2021

Substance P-induced lung inflammation in mice is mast cell dependent.

Clin Exp Allergy 2021 May 17. Epub 2021 May 17.

School of Pharmacy, Health Science Center, Jiaotong University, 710061, China.

Background: Allergic asthma is a common inflammatory lung disease and a major health problem worldwide. Mast cells (MCs) play a key role in the early stage pathophysiology of allergic asthma. Substance P (SP) functions in neurogenic inflammation by activating MCs, and therefore it may to participate in the occurrence and development of asthma.

Objective: We examined the relationship between SP and lung inflammation, and also whether SP can directly trigger asthma.

Methods: We measured the number of peripheral blood eosinophils, neutrophils, and basophils and evaluated the levels of IgE and SP in blood samples of 86 individuals with allergic asthma. Serum IgE and SP levels were also determined in 29 healthy individuals. C57BL/6 mice were subjected to different doses of SP and bronchoalveolar lavage fluid (BALF) was collected to count the inflammatory cells. Lung tissues were analyzed using histopathological methods to evaluate lung peribronchial inflammation, fibrosis, and glycogen deposition. Levels of IgE, interleukin (IL)-1, IL-2, IL-4, IL-5, IL-13, IL-17 and IFN-γ were determined in mice serum.

Results: SP levels were increased in the serum samples of patients with asthma. SP induced mouse lung peribronchial inflammation, fibrosis, and glycogen deposition, with high levels of Th2-related cytokines such as IL-4, IL-5, and IL-13 observed in the BALF. Furthermore, low level of total IgE was noted in the serum, and SP had little effect on MC-deficient kit mice.

Conclusions & Clinical Relevance: SP levels increased significantly in serum of asthmatic patients and independently associated with the risk of asthma. Furthermore, SP induced Th2 lung inflammation in mice, which was dependent on MCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cea.13902DOI Listing
May 2021

The endoribonuclease N4BP1 prevents psoriasis by controlling both keratinocytes proliferation and neutrophil infiltration.

Cell Death Dis 2021 May 14;12(5):488. Epub 2021 May 14.

Department of Pathogenic Biology, School of Medicine, Nantong University, 226001, Jiangsu, China.

Psoriasis is a common chronic skin disease, characterized by abnormal interplay between hyperproliferative epidermal keratinocytes and self-reactive immune cells with not fully addressed molecular mechanism. N4BP1 (NEDD4-binding protein 1) is considered as an immune regulator for a long time but its physiological role is not determined yet. Here, we found that the expression of N4BP1 in skin was highest among all 54 tested tissues, and its expression was further upregulated in psoriatic skin. N4BP1-deficient mice exhibited normal grossly, but developed severe and prolonged IMQ-induced psoriasis-like disease comparing to controls. N4BP1 mainly expressed in keratinocytes and located on nucleus. Up- but not downregulated genes in N4BP1-deficient skin were specifically enriched in keratinocyte proliferation and differentiation. The proliferation of N4BP1-deficient primary keratinocytes was faster compared to that of controls. The upregulated genes upon ablation of N4BP1 were highly enriched in targets of AP-1 transcription factor. Knocking out N4BP1 resulted in upregulation of JunB and FosB, and conversely, overexpression of N4BP1 greatly reduced their expression. Furthermore, N4BP1 binds with JunB and FosB encoding mRNAs and greatly reduces their stability. In addition, with a high expression in neutrophils, N4BP1 limits survival of neutrophils in blood and infiltration of neutrophils in psoriatic skin by targeting CXCL1, CCL20, and S100A8. These findings demonstrate that N4BP1 controls the proper function of keratinocytes and neutrophils by negatively regulating JunB, FosB, and CXCL1, respectively, and that is critical for psoriasis prevention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-021-03774-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121926PMC
May 2021

Cryptotanshinone Inhibits ERα-Dependent and -Independent BCRP Oligomer Formation to Reverse Multidrug Resistance in Breast Cancer.

Front Oncol 2021 22;11:624811. Epub 2021 Apr 22.

Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.

Both long-term anti-estrogen therapy and estrogen receptor-negative breast cancer contribute to drug resistance, causing poor prognosis in breast cancer patients. Breast cancer resistance protein (BCRP) plays an important role in multidrug resistance. Here, we show that cryptotanshinone (CPT), an anti-estrogen compound, inhibited the oligomer formation of BCRP on the cell membrane, thus blocking its efflux function. The inhibitory effect of CPT on BCRP was dependent on the expression level of estrogen receptor α (ERα) in ERα-positive breast cancer cells. Furthermore, ERα-negative breast cancer cells with high expression of BCRP were also sensitive to CPT because CPT was able to bind to BCRP and inhibit its oligomer formation on the cell membrane, suggesting that the high level of BCRP expression is crucial for CPT to reverse drug resistance. The combination of CPT and chemotherapeutic agents displayed enhanced anticancer effects. The results suggest that CPT is a novel BCRP inhibitor blocking the oligomer formation of BCRP on the cell membrane. CPT is able to inhibit the activity of BCRP in an ERα-dependent and -independent manner, sensitizing breast cancer cells to chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.624811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100513PMC
April 2021

Rare and favorable prognosis of pediatric acute lymphoblastic leukemia with TLS-ERG fusion gene: Case report with long-term follow-up and review of literature.

Cancer Genet 2021 Apr 10;256-257:51-56. Epub 2021 Apr 10.

Department/Center of Hematology-oncology, Diagnostic and Treatment Center for Childhood Leukemia of Zhejiang Province, Children's Hospital of Zhejiang University School of Medicine, National Medical Research Center for Child Health, #57 Zhuganxiang Road, Yan-an Street, Hangzhou 310003, China. Electronic address:

In the study of acute myeloid leukemia (AML), TLS-ERG (also called FUS-ERG or TLS/FUS-ERG) was found to be closely associated with extramedullary disease (EMD), with very poor prognosis. However, the occurrence of TLS-ERG in acute lymphoblastic leukemia (ALL) is very rare. Till date, only 20 cases of ALL with TLS-ERG gene have been reported, of which six are children. Therefore, many clinical aspects of ALL with TLS-ERG gene remain unknown. The aim of this study was to report the clinical features and outcomes of four TLS-ERG-positive pediatric ALL cases. The results showed that all four pediatric patients with this fusion gene achieved an excellent outcome even with a very short-term induction chemotherapy of less than two months. These findings indicated that children with TLS-ERG-positive ALL have very low risk of leukemia, and can be treated and cured with less intensive chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cancergen.2021.04.003DOI Listing
April 2021

Early-senescent bone marrow mesenchymal stem cells promote C2C12 cell myogenic differentiation by preventing the nuclear translocation of FOXO3.

Life Sci 2021 Jul 19;277:119520. Epub 2021 Apr 19.

Department of Pain, Huadong Hospital, Shanghai Key Laboratory of Clinical Geriatric Medicine, Fudan University, Shanghai, China. Electronic address:

Aims: Mouse bone marrow mesenchymal stem cells (BMSCs) are pluripotent cells with self-renewal and differentiation abilities. Since the effects of senescent BMSCs on C2C12 cells are not fully clear, the present study aimed to elucidate these effects.

Main Methods: Senescence-associated β-galactosidase staining and western blotting were performed to confirm the senescence of BMSCs. Immunofluorescence and western blotting were used to assess myoblast differentiation in each group. The role of the AKT/P70 signaling pathway and forkhead box O3 (FOXO3) nuclear translocation was explored by western blotting. BMSC-derived exosomes were injected into the tibialis anterior of mice, and RT-qPCR was used to assess the role of exosomes in promoting muscle differentiation.

Key Findings: Conditioned medium (CM) from early-senescent BMSCs promoted myogenic differentiation in vitro, which was detected as enhanced expression of myosin heavy chain (MHC), myogenin (MYOG), and myogenic differentiation 1 (MyoD). The AKT signaling pathway was found to be regulated by CM, which inhibited FOXO3 nuclear translocation. RT-qPCR analysis results showed that MHC, MyoD, and MYOG mRNA expression increased in the tibialis anterior of mice after exosome injection.

Significance: The present study demonstrated that early-senescent BMSCs accelerated C2C12 cell myogenic differentiation, and the transcription factor, FOXO3, was the target of senescent cells. Collectively, our results suggest that the AKT/P70 signaling pathway mediates the effect of BMSCs on neighboring cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lfs.2021.119520DOI Listing
July 2021

Difference in Moxibustion-Induced Microcirculatory Responses between the Heart and Lung Meridians Assessed by Laser Doppler Flowmetry.

Evid Based Complement Alternat Med 2021 1;2021:6644625. Epub 2021 Apr 1.

Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Hangzhou 310053, China.

Objective: By comparing the differences in microcirculatory responses of the heart and lung meridians induced by moxibustion on these two meridians, respectively, this study aimed to investigate the specificity for site-to-site association on body surface between different meridians.

Methods: Eighty healthy adults were enrolled and divided into the lung meridian intervention group and heart meridian intervention group in a ratio of 1 : 1. Three-channel laser Doppler flowmetry was used to monitor microcirculatory responses for the heart and lung meridians. Primary outcome was change of blood perfusion units (PU) of three measurement sites along the two meridians.

Results: In the lung meridian intervention group, following moxibustion performed at LU5 of the lung meridian, PU in the distal site of the lung meridian increased significantly. By contrast, the PU of HT3 in the heart meridian, which was nearest to the moxibustion site, did not change significantly. PU in the distal site of the heart meridian declined. Meanwhile, significant difference in PU change was detected between the distal site of the lung meridian and the other two control sites of the heart meridians during moxibustion and postmoxibustion. Alternatively, similar to the results of the lung meridian intervention group, the specificity of microcirculatory response between the heart and lung meridians was observed in the heart meridian intervention group.

Conclusions: For the heart and lung meridians, the effect of moxibustion-induced microcirculatory response may be more related to meridian routes than the specific distance between two sites located at different meridians, thereby supporting possible specificity for site-to-site association on the body surface between these two meridians. Nevertheless, given that only two meridians and limited measurement sites were compared, all current findings are not sufficiently robust. Further research should be conducted to investigate more meridians and measurement sites.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/6644625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032512PMC
April 2021

A survey of postpartum depression and health care needs among Chinese postpartum women during the pandemic of COVID-19.

Arch Psychiatr Nurs 2021 04 17;35(2):172-177. Epub 2021 Feb 17.

West China School of Nursing/West China Hospital, Sichuan University, Chengdu, Sichuan, China. Electronic address:

Background: The COVID-19 pandemic seriously endangers the public's mental health, especially to pregnant and postpartum women. But little is known about postpartum depression and health care needs among Chinese postpartum women.

Aim: To investigate the status and risk factors of postpartum depression and health care needs among Chinese postpartum women during the COVID-19 pandemic.

Methods: In this cross-sectional study, 209 Chinese postpartum women were recruited from May to July 2020 by convenience sampling and assessed online with self-designed Maternal General Information Questionnaire, Edinburgh Postpartum Depression Scale (EPDS) and Chinese Version of the Perceived Stress Scale (CPSS). Descriptive statistics, chi-square test, independent samples t-test, one-way ANOVA, Pearson correlation and multiple linear regression were used for data analysis.

Results: With the EPDS cut-off value of 10, the incidence of postpartum depressive symptoms was 56.9%. Age, history of abortion and perceived stress were the influencing factors of postpartum depression (adjusted R = 0.432, F = 23.611, p < .001). The top three health care needs were infant rearing guidance (78.0%), maternal and infant protection guidance (60.3%) and dietary guidance (45.0%). The proportion of psychological rehabilitation guidance needs in the depressed group was significantly higher than that in the non-depressed group (34.5% vs. 20.0%, p < .05).

Conclusions: Maternal postpartum depression in China was at a high level during the COVID-19 pandemic. Women aged 25-34, with a history of abortion and high stress levels were at higher risk for postpartum depression. Timely psychological counselling, intervention and COVID-19-related health education are in great need for postpartum women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.apnu.2021.02.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886635PMC
April 2021

Lyophilized powder of mesenchymal stem cell supernatant attenuates acute lung injury through the IL-6-p-STAT3-p63-JAG2 pathway.

Stem Cell Res Ther 2021 Mar 29;12(1):216. Epub 2021 Mar 29.

Department of Pulmonary and Critical Care Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

Background: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are syndromes of acute respiratory failure with extremely high mortality and few effective treatments. Mesenchymal stem cells (MSCs) may reportedly contribute to tissue repair in ALI and ARDS. However, applications of MSCs have been restricted due to safety considerations and limitations in terms of large-scale production and industrial delivery. Alternatively, the MSC secretome has been considered promising for use in therapeutic approaches and has been advanced in pre-clinical and clinical trials. Furthermore, the MSC secretome can be freeze-dried into a stable and ready-to-use supernatant lyophilized powder (SLP) form. Currently, there are no studies on the role of MSC SLP in ALI.

Methods: Intratracheal bleomycin was used to induce ALI in mice, and intratracheal MSC SLP was administered as a treatment. Histopathological assessment was performed by hematoxylin and eosin, immunohistochemistry, and immunofluorescence staining. Apoptosis, inflammatory infiltration, immunological cell counts, cytokine levels, and mRNA- and protein-expression levels of relevant targets were measured by performing terminal deoxynucleotidyl transferase dUTP nick-end labeling assays, determining total cell and protein levels in bronchoalveolar lavage fluids, flow cytometry, multiple cytokine-detection techniques, and reverse transcriptase-quantitative polymerase chain reaction and western blot analysis, respectively.

Results: We found that intratracheal MSC SLP considerably promoted cell survival, inhibited epithelial cell apoptosis, attenuated inflammatory cell recruitment, and reversed immunological imbalances induced by bleomycin. MSC SLP inhibited the interleukin 6-phosphorylated signal transducer and activator of transcription signaling pathway to activate tumor protein 63-jagged 2 signaling in basal cells, suppress T helper 17 cell differentiation, promote p63 cell proliferation and lung damage repair, and attenuate inflammatory responses.

Conclusions: MSC SLP ameliorated ALI by activating p63 and promoting p63 cell proliferation and the repair of damaged epithelial cells. The findings of this study also shed insight into ALI pathogenesis and imply that MSC SLP shows considerable therapeutic promise for treating ALI and ARDS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13287-021-02276-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008635PMC
March 2021

Elevated TEFM expression promotes growth and metastasis through activation of ROS/ERK signaling in hepatocellular carcinoma.

Cell Death Dis 2021 03 26;12(4):325. Epub 2021 Mar 26.

Nanyang central Hospital, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, China.

TEFM (transcription elongation factor of mitochondria) has been identified as a novel nuclear-encoded transcription elongation factor in the transcription of mitochondrial genome. Our bioinformatics analysis of TCGA data revealed an aberrant over-expression of TEFM in hepatocellular carcinoma (HCC). We analyzed its biological effects and clinical significance in this malignancy. TEFM expression was analyzed by quantitative real-time PCR, western blot, and immunohistochemistry analysis in HCC tissues and cell lines. The effects of TEFM on HCC cell growth and metastasis were determined by cell proliferation, colony formation, flow cytometric cell cycle and apoptosis, migration, and invasion assays. TEFM expression was significantly increased in HCC tissues mainly caused by down-regulation of miR-194-5p. Its increased expression is correlated with poor prognosis of HCC patients. TEFM promoted HCC growth and metastasis both in vitro and in vivo by promoting G1-S cell transition, epithelial-to-mesenchymal transition (EMT), and suppressing cell apoptosis. Mechanistically, TEFM exerts its tumor growth and metastasis promoting effects at least partly through increasing ROS production and subsequently by activation of ERK signaling. Our study suggests that TEFM functions as a vital oncogene in promoting growth and metastasis in HCC and may contribute to the targeted therapy of HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-021-03618-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997956PMC
March 2021

Association between preoperative serum TSH and tumor status in patients with papillary thyroid microcarcinoma.

Endocrine 2021 Mar 23. Epub 2021 Mar 23.

Department of Head and Neck Surgery, Gansu Provincial Cancer Hospital, Lanzhou, 730050, China.

Thyroid-stimulating hormone (TSH) is a growth factor affecting the initiation or progression of papillary thyroid cancer (PTC). However, the relationship between preoperative serum TSH and papillary thyroid microcarcinoma (PTMC) remains controversial. To investigate the relationship between preoperative serum TSH and tumor status of PTMC, a multicentered retrospective study was performed from January 2014 to December 2016. The cohort of this study consisted of 1997 patients who underwent thyroid surgery. Serum TSH concentrations were measured and PTMC was diagnosed based on the post-operation pathological report. Results showed that the preoperative serum TSH concentration was not related to age and gender but was positively associated with tumor size. Furthermore, higher TSH level was associated with extra-thyroidal extension and lymph node metastasis (LNM). These results indicated that TSH might not be involved in the development of PTMC but may be associated with PTMC progression. Preoperative serum TSH concentration should be considered as risk predictor for tumor progression in patients with PTMC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12020-021-02690-5DOI Listing
March 2021

MiR-1290 promotes myoblast differentiation and protects against myotube atrophy via Akt/p70/FoxO3 pathway regulation.

Skelet Muscle 2021 Mar 15;11(1). Epub 2021 Mar 15.

Department of Pain, Huadong Hospital, Shanghai Key Laboratory of Clinical Geriatric Medicine, Fudan University, No. 221, West YanAn Rd, Shanghai, 200040, P.R. China.

Background: Sarcopenia is a common skeletal disease related to myogenic disorders and muscle atrophy. Current clinical management has limited effectiveness. We sought to investigate the role of miR-1290 in myoblast differentiation and muscle atrophy.

Methods: By transfecting miR-1290 into C2C12 cells, we investigated whether miR-1290 regulates myogenesis and myotube atrophy via AKT/P70 signaling pathway. MHC staining was performed to assess myoblast differentiation. Differentiation-related MHC, Myod, and Myog protein levels, and atrophy-related MuRF1 and atrogin-1 were explored by western blot. An LPS-induced muscle atrophy rat model was developed. RT-PCR was conducted to analyze miR-1290 serum levels in muscle atrophy patients and normal controls (NCs).

Results: The miR-1290 transfection increased MHC-positive cells and MHC, Myod, and Myog protein levels in the miR-1290 transfection group, demonstrating that miR-1290 promoted C2C12 myoblast differentiation. Myotube diameter in the miR-1290 transfection group was higher than in the TNF-α-induced model group. Western blot analysis showed decreased MuRF1 and atrogin-1 levels in the miR-1290 transfection group compared with the model group, demonstrating that miR-1290 protected against myoblast cellular atrophy. Luciferase assay and western blot analysis showed that miR-1290 regulation was likely caused by AKT/p70/FOXO3 phosphorylation activation. In the LPS-induced muscle atrophy rat model, miR-1290 mimics ameliorated gastrocnemius muscle loss and increased muscle fiber cross-sectional area. Clinically, miR-1290 serum level was significantly decreased in muscle atrophy patients.

Conclusions: We found that miR-1290 enhances myoblast differentiation and inhibits myotube atrophy through Akt/p70/FoxO3 signaling in vitro and in vivo. In addition, miR-1290 may be a potential therapeutic target for sarcopenia treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13395-021-00262-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958887PMC
March 2021

Epidural analgesia during labor and its optimal initiation time-points: A real-world study on 400 Chinese nulliparas.

Medicine (Baltimore) 2021 Mar;100(9):e24923

Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.

Abstract: Recent research has suggested that 6 cm of cervical dilation should be the threshold for the active labor phase, and it has confirmed that epidural analgesia (EA) is a safe method of pain relief during labor. However, the evidence provided for these findings comes mainly from randomized controlled clinical trials (RCTs), which suffer from the limitation of real-world generalizability.To test the generalizability of the conclusions from these previous RCTs, we conducted a prospective cohort, real-world study (RWS) on 400 Chinese term nulliparas. A total of 200 of the participants (the EA group) received EA upon request. The participants in the EA group were further subdivided as follows according to their cervical dilation when the EA administration was initiated (CDE): [EA1 group (CDE < 3 cm), EA2 group (3 cm ≤ CDE < 6 cm), and EA3 group (CDE ≥ 6 cm)]. We compared the labor duration of the EA group versus the non-EA (NEA) group, and the NEA group versus the 3 EA subgroups. We also compared delivery outcomes between the EA and NEA groups.The median total labor duration for the EA group [676 (511-923) minutes] was significantly longer than that of the NEA group [514 (373-721) minutes] (P < 0.001). The median durations of both the first- and second-stages of labor for the EA group [600 (405-855) minutes, 68 (49-97) minutes] were longer than those of the NEA group [420 (300-630) minutes, 50 (32-85) minutes] (P < .001, P < .001)]. In addition, the median total labor durations in both the EA1 [720 (548-958) minutes] and EA2 groups [688 (534-926) minutes] were longer than in the NEA group (P < .001 and P < .001, respectively), and the first- and second-stage labor durations of these subgroups were similar to their total labor durations. A Cox regression analysis showed that EA was associated with longer first-stage labor [hazard ratio (HR) 0.55, 95% confidence interval (CI) 0.42-0.71, P < .001] and longer second-stage labor (HR 0.66, 95% CI 0.51-0.85, P = .001). The delivery modes and neonatal outcomes between the EA and NEA groups were not statistically different, however.Our findings suggest that EA administered before a cervical dilation of 6 cm may be associated with longer total, first-, and second-stage labor durations compared with no EA, while later EA administration is not. In addition, though EA prolongs labor duration, it does not impact delivery outcomes. These results confirm the significance of a 6 cm cervical dilation threshold in real-world labor settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000024923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939169PMC
March 2021

Solid-State Nuclear Magnetic Resonance Identifies Abnormal Calcium Phosphate Formation in Diseased Bones.

ACS Biomater Sci Eng 2021 03 22;7(3):1159-1168. Epub 2021 Feb 22.

Center for Chemistry of High-Performance & Novel Materials, Department of Chemistry, Zhejiang University, Hangzhou 310027, People's Republic of China.

The crystallites of calcium phosphate (CaP) in bones consist of hydroxyl apatite (HA) and amorphous calcium phosphate (ACP). These nanoscale structures of CaP are sculptured by biological bone formation and resorption processes and are one of the crucial factors that determine the overall strength of the constructs. We used one- and two-dimensional H-P solid-state nuclear magnetic resonance (SSNMR) to investigate the nanoscopic structural changes of CaP. Two quantitative measurables are deduced based on the heterogeneous linewidth of P signal and the ratio of ACP to HA, which characterize the mineral crystallinity and the relative proportion of ACP, respectively. We analyzed bones from different murine models of osteopetrosis and osteoporosis and from human samples with osteoporosis and osteoarthritis. It shows that the ACP content increases notably in osteopetrotic bones that are characterized by defective osteoclastic resorption, whereas the overall crystallinity increases in osteoporotic bones that are marked by overactive osteoclastic resorption. Similar pathological characteristics are observed for the sclerotic bones of late-stage osteoarthritis, as compared to those of the osteopetrotic bones. These findings suggest that osteoclast-related bone diseases not only alter the bone density macroscopically but also lead to abnormal formation of CaP crystallites. The quantitative measurement by SSNMR provides a unique perspective on the pathology of bone diseases at the nanoscopic level.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsbiomaterials.0c01559DOI Listing
March 2021

Involvement of miR-619-5p in resistance to cisplatin by regulating ATXN3 in oral squamous cell carcinoma.

Int J Biol Sci 2021 1;17(2):430-447. Epub 2021 Jan 1.

Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.

MicroRNAs are major post-transcriptional regulators responsible for the development of human cancers, including OSCC. The specific role of miR-619-5p in OSCC, however, is rarely reported. Cisplatin is one of the mostly applied chemotherapy drugs of OSCC. Nevertheless, drug resistance of cisplatin following the initial chemotherapy largely restricts its clinical benefits, and the mechanism of cisplatin resistance is unclear. This study intends to explore the biological function of miR-619-5p in the development of cisplatin resistance in OSCC cell lines and a xenograft model, as well as the potential molecular mechanism. Our results showed that miR-619-5p was down-regulated in OSCC samples and cisplatin-resistant OSCC cells. Ectopically expressed miR-619-5p inhibited proliferative, migratory and invasive abilities of OSCC cisplatin-resistant cells. The putative target gene ATXN3 was predicted by bioinformatic analysis and confirmed by dual-luciferase reporter assay. Importantly, ATXN3 was responsible for the regulatory effects of miR-619-5p on biological behaviors of cisplatin-resistant OSCC cells. Moreover, miR-619-5p mimics and ATXN3-siRNA significantly enhanced ATXN3 knockdown in both HN6/CDDPR and CAL27/CDDPR cells and inhibited expression of PI3K and AKT. evidences demonstrated that intratumoral injection of miR-619-5p agomir remarkably slowed down the growth of OSCC in xenograft mice. Collectively, microRNA-619-5p was the vital regulator for regulating cisplatin resistance of OSCC, which may be served as a potential therapeutic target.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/ijbs.54014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893581PMC
January 2021

The difference in heat transport characteristics of the heart and lung meridians: A comparative study of COPD patients and healthy subjects.

Medicine (Baltimore) 2021 Feb;100(5):e23804

Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Hangzhou, China.

Background: The vast majority of previous studies focused on the relationship between 1 meridian and 1 organ, and the comparison and specificity between 2 meridians is rarely explored. Thus, the aim of this study is to compare the heat transport characteristics between 2 different meridians and the specificity between them will also be investigated.

Methods: The Lung and Heart meridians are chosen for comparison of 2 different meridians. We will enroll 120 subjects and divide them into the healthy control group, chronic obstructive pulmonary disease (COPD) group and healthy intervention group, in a 1:1:1 ratio. Infrared thermography (IRT) will be used to assess the heat transport characteristics of the Heart and Lung meridians. The specificity for the meridian-visceral association will be investigated by comparing the difference in heat transport characteristic between the Heart and Lung meridians in the healthy control group and COPD group. Meanwhile, moxibustion will be given to subjects in the Heart meridian and Lung meridian respectively in the healthy intervention group to verify the specificity for the surface-surface association.

Results: The primary outcomes will be the temperature of corresponding sites along the Heart and Lung meridians.

Conclusion: This study will verify the specificity between different meridians by comparing the difference in heat transport characteristic. The findings will guide the selection of acupoints to optimize the therapeutic effect of acupuncture and help determine whether IRT could be used to assist in the diagnosis of COPD.

Ethics And Dissemination: The study has been approved by the Third Affiliated Hospital of Zhejiang Chinese Medical University (Approval No. ZSLL-KY-2019-001G-01).

Trial Registration Numbers: NCT04046588.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000023804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870227PMC
February 2021

Alternative Splicing of Heat Shock Transcription Factor 2 Regulates the Expression of Laccase Gene Family in Response to Copper in .

Appl Environ Microbiol 2021 Feb 12. Epub 2021 Feb 12.

Laboratory of Bioconversion, Life Science and Technology College, Kunming University of Science and Technology, Kunming, 650500, PR China

White-rot fungi, especially strains, are the primary source of industrial laccases in bioenergy and bioremediation. strains express members of the laccase gene family with different physicochemical properties and expression patterns. However, the literature on the expression pattern of the laccase gene family in S0301 and the response mechanism to Cu, a key laccase inducer, in white-rot fungal strains is scarce. In the present study, we found that Cu could induce the mRNAs and proteins of the two alternative splicing variants of heat shock transcription factor 2 (). Furthermore, the overexpression of alternative splicing variants and in the homokaryotic S0301 strain showed opposite effects on the extracellular total laccase activity, with the maximum laccase activity of approximately 0.6 U mL and 3.0 U mL, respectively, on the eighth day, which is 0.4 and 2.3 times that of the wild type strain. Similarly, TtHSF2α and TtHSF2β-I play opposite roles in the oxidation tolerance to HO In addition, the direct binding of TtHSF2α to the promoter regions of the representative laccase isoenzymes ( and ) and protein-protein interactions between TtHSF2α and TtHSF2β-I were detected. Our results demonstrate the crucial roles of and its alternative splicing variants in response to Cu We believe that these findings will deepen our understanding of alternative splicing of HSFs and their regulatory mechanism of the laccase gene family in white-rot fungi. The members of laccase gene family in strains are the primary source of industrial laccase and have gained widespread attention. Increasing the yield and enzymatic properties of laccase through various methods has always been a topic worthy of attention, and there is no report on the regulation of laccase expression through HSF transcription factor engineering. Here, we found that two alternative splicing variants of functioned oppositely in regulating the expression of laccase genes, and copper can induce the expression of almost all members of the laccase gene family. Most importantly, our study suggested that and its alternative splicing variants are vital for copper-induced production of laccases in S0301.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/AEM.00055-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091107PMC
February 2021

Antiglaucoma Potential of β-Glucogallin Is Mediated by Modulating Mitochondrial Responses in Experimentally Induced Glaucoma.

Neuroimmunomodulation 2021 Feb 11:1-10. Epub 2021 Feb 11.

Department of Ophthalmology, Cangzhou Central Hospital, Cangzhou, China.

Background: The use of phytochemicals for the treatment of various bodily ailments has been in practice since ancient days. Even though in practice, scientific studies on the protective effect of β-glucogallin (BG) against glaucoma is limited.

Objectives: In the present study, the in vitro glaucoma model (hydrostatic pressure) using PC12 neuronal cells exposed to BG were used to elucidate its protective effects.

Method: The cultured cells were analyzed for the mitochondrial responses, oxidant-antioxidant status, and expression of caveolin-1, ANGPTL7, the glaucoma markers, and cytokines.

Results: We demonstrated a significant increase in the expression of glial fibrillary acidic protein, ANGPTL7, with altered mitochondrial enzymes in glaucoma cells compared to the control. Moreover, cells predisposed to hydrostatic pressure demonstrated an increase in oxidative stress with augmented (p < 0.01) inflammatory cytokines such as IL-2, CXCR4, IL-6, IL-8, MCP-1, and TNF-α. On the other hand, cells pretreated with BG attenuated the reactive oxygen species levels with improved antioxidant enzymes. Simultaneously, the levels of inflammatory cytokines and ANGPTL7 proteins were found attenuated with restored mitochondrial responses in BG pretreated cells.

Conclusion: Thus, the results of the present study demonstrate that the use of BG on retinal cells against relieving the intraocular pressure may be a promising therapeutic for controlling the disease progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000512992DOI Listing
February 2021

Cryo-EM structures reveal the molecular basis of receptor-initiated coxsackievirus uncoating.

Cell Host Microbe 2021 03 3;29(3):448-462.e5. Epub 2021 Feb 3.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, China; Research Unit of Frontier Technology of Structural Vaccinology, Chinese Academy of Medical Sciences, Xiamen, Fujian 361102, China. Electronic address:

Enterovirus uncoating receptors bind at the surface depression ("canyon") that encircles each capsid vertex causing the release of a host-derived lipid called "pocket factor" that is buried in a hydrophobic pocket formed by the major viral capsid protein, VP1. Coxsackievirus and adenovirus receptor (CAR) is a universal uncoating receptor of group B coxsackieviruses (CVB). Here, we present five high-resolution cryoEM structures of CVB representing different stages of virus infection. Structural comparisons show that the CAR penetrates deeper into the canyon than other uncoating receptors, leading to a cascade of events: collapse of the VP1 hydrophobic pocket, high-efficiency release of the pocket factor and viral uncoating and genome release under neutral pH, as compared with low pH. Furthermore, we identified a potent therapeutic antibody that can neutralize viral infection by interfering with virion-CAR interactions, destabilizing the capsid and inducing virion disruption. Together, these results define the structural basis of CVB cell entry and antibody neutralization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chom.2021.01.001DOI Listing
March 2021

Effect of Shenzhu Tiaopi granule on hepatic insulin resistance in diabetic Goto-Kakizakirats via liver kinase B1/adenosine 5'-monophosphate/mammalian target of rapamycin signaling pathway.

J Tradit Chin Med 2021 02;41(1):107-116

Anhui University of Chinese Medicine, Hefei 230031, China.

Objective: To observe the therapeutic effect of Shenzhu Tiaopi granule (, STG) on insulin resistance (IR) in the liver of diabetic Goto-Kakizaki (GK) rat and investigate underlying mechanisms.

Methods: Ten 12-week-old male Wistar rats were assigned as normal control (NC) group, while 40 12-week-old male specific-pathogen-free GK rats were randomly divided into four experimental groups, 10 diabetic rats each. Animals were fed with a normal diet. Fasting blood glucose (FBG), water intake, and body weight were recorded during 6 weeks of daily single-dose treatment: STG low-dose group, 4.5 g/kg (STG-L); STG high-dose group,9 g/kg (STG-H); metformin group, 0.1 g/kg (MET); model control (MC) and NC groups, equal volume of 0.9% NaCl solution. The serum fasting insulin (FINS), C-Peptide and IR index (HOMA-IR) were detected every 2 weeks during treatment and glucose tolerance was measured in the 3rd day before the material was taken. After the 6-week STG treatment, Liver tissues were processed for hematoxylin-eosin staining to perform light microscopy analysis and for assessing expression and distribution of insulin receptor substrates (IRS-1) and glucose transporter (GLUT-4) by immunohistochemistry analysis. Expression levels of liver kinase B1 (LKB1) / adenosine 5'-monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway proteins, including LKB1, phospho-AMPK (p-AMPK)/AMPK, phospho-mTOR (p-mTOR)/mTOR, and ribosomal protein S6 kinase polypeptide 1 (S6K1),were detected by Western blotting.

Results: STG significantly reduced the FBG level and liver fat deposition in diabetic GK rats. After STG treatment completion, FINS, HOMA-IR, C-Peptide and area under blood glucose curve (AUC) were lower in STG groups than in the MC group, indicating that IR was reduced and liver fat lesions were resolved. In liver tissues, STG groups displayed significantly higher IRS-1 and GLUT-4 expression than the MC group, along with increasedLKB1 and p-AMPK/AMPK expression and decreased p-mTOR/mTOR and phospho-S6K1expression, suggesting that STG stimulatedLKB1 activation of AMPK and suppressed them TOR/S6K1 downstream pathway.

Conclusion: Growing GK rats developed hepatic IR, but STG treatment significantly improved hyperglycemia and IR and resolved hepatic fatty lesions. Interestingly, STG treatment stimulated the expression of IRS-1 and GLUT-4 in the liver of diabetic GK rats, indicating a potential involvement in the regulation of theLKB1/AMPK/mTOR signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.19852/j.cnki.jtcm.2021.01.013DOI Listing
February 2021

Electroacupuncture Alleviates Chronic Pain-Induced Anxiety Disorders by Regulating the rACC-Thalamus Circuitry.

Front Neurosci 2020 11;14:615395. Epub 2021 Jan 11.

Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.

Anxiety is a common comorbidity associated with chronic pain, which results in chronic pain complexification and difficulty in treatment. Electroacupuncture (EA) is commonly used to treat chronic pain and anxiety. However, the underlying mechanisms of the EA effect are largely unknown. Here, we showed that a circuitry underlying chronic pain induces anxiety disorders, and EA can treat them by regulating such circuitry. Using chemogenetic methods, we found that chemogenetic activation of the rostral anterior cingulate cortex (rACC) glutamatergic output to the thalamus induced anxiety disorders in control rats. Then, chemogenetic inhibition of the rACC-thalamus circuitry reduced anxiety-like behavior produced by intraplantar injection of the complete Freund's adjuvant (CFA). In this study, we examined the effects of EA on a rat model of CFA-mediated anxiety-like behaviors and the related mechanisms. We found that chemogenetic activation of the rACC-thalamus circuitry effectively blocked the effects of EA on chronic pain-induced anxiety-like behaviors in CFA rats. These results demonstrate an underlying rACC-thalamus glutamatergic circuitry that regulates CFA-mediated anxiety-like behaviors. This study also provides a potential mechanistic explanation for EA treatment of anxiety caused by chronic pain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnins.2020.615395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829552PMC
January 2021

Amentoflavone Ameliorates Memory Deficits and Abnormal Autophagy in Aβ-Induced Mice by mTOR Signaling.

Neurochem Res 2021 Apr 25;46(4):921-934. Epub 2021 Jan 25.

Henan University of Chinese Medicine, Zhengzhou, China.

Alzheimer's disease (AD) is a neurodegenerative disease in which autophagy plays a crucial role. Amentoflavone is a flavonoid obtained from various plants and has been shown to have AD-resistant neuroprotective effects. This study investigated the role of amentoflavone on memory impairment and abnormal autophagy in amyloid-β25-35 (Aβ)-induced mice to elucidate the mechanisms by which it exerts neuroprotective effects. In this experiment, the AD mouse model was established by intracerebroventricular (ICV) injection of Aβ peptides, and amentoflavone was administered orally for 4 weeks. Behavioral changes in mice and pathological changes in the hippocampus were observed, and levels of inflammation, oxidative stress, and autophagy in the brain were detected and analyzed. PC-12 and APPswe-N2a cells were used in vitro to further investigate the effect of amentoflavone on the level of intracellular autophagy. Molecular docking was used to determine the action sites of amentoflavone. The results showed that amentoflavone improved memory function, eased anxiety symptoms in Aβ-induced mice, and reduced atrophic degeneration of neurons in the hippocampus. Moreover, amentoflavone lessened the oxidative stress and inflammation in the brains of mice. Through in vivo and in vitro experiments, we found that amentoflavone may enhance autophagy, by way of binding to the ATP site of the mTOR protein kinase domain. Amentoflavone not only interacted with mTOR, but also improved Aβ-induced cognitive dysfunction in mice by enhancing autophagy, attenuating levels of inflammation and oxidative stress, and reducing apoptosis in brain cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11064-020-03223-8DOI Listing
April 2021

Sufentanil preconditioning protects against myocardial ischemia/reperfusion injury via miR-125a/DRAM2 axis.

Cell Cycle 2021 02 21;20(4):383-391. Epub 2021 Jan 21.

Department of Anesthesiology, The First Hospital Affiliated to Jinzhou Medical University , Jinzhou, P.R. China.

This project aimed to investigate the protective mechanism of sufentanil pretreatment on myocardial ischemia-reperfusion injury (IRI). An rat model of myocardial IRI and an cultured cardiomyocyte model of hypoxia-reoxygenation (H/R) were used to confirm the anti-oxidation and anti-autophagy effects of sufentanil. The interaction between miR-125a and damage-regulated autophagy regulator 2 (DRAM2) was verified by luciferase reporter assay. We showed that pretreatment with sufentanil suppressed myocardial damage caused by IRI in rats by inhibiting oxidative stress and mitochondrial autophagy. Furthermore, the cardioprotective mechanism of sufentanil was mediated by miR-125a. MiR-125a targeted DRAM2 to ameliorate cardiomyocyte autophagy and oxidative injury following H/R treatment. In conclusion, our results demonstrated that sufentanil pretreatment produced a protective effect against myocardial IRI via regulating miR-125a/DRAM2 signaling axis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15384101.2021.1875668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894415PMC
February 2021

Exposure to particulate matter 2.5 and cigarette smoke induces the synthesis of lipid droplets by glycerol kinase 5.

Clin Exp Pharmacol Physiol 2021 Apr 18;48(4):498-507. Epub 2021 Jan 18.

Department of Pulmonary Medicine, Pudong Hospital Affiliated to Fudan University, Shanghai, China.

Particulate matter (PM2.5) and cigarette smoke exposure are leading factors contributing to various diseases, especially respiratory diseases. The purpose of this research was to study the effects of PM2.5 and cigarette smoke on glycerol kinase 5 (GK5) expression and the possible mechanisms by which GK5 participates in lipid droplet (LD) synthesis in alveolar epithelial A549 cells. Real-time polymerase chain reaction (RT-PCR) and western blotting have been used for the detection of messenger RNA (mRNA) and protein expression respectively. GK5 overexpressing cells were established by lentivirus transfection, whereby lentiviral vectors deliver the gene into chromosomes, allowing stable expression. Affymetrix microarray analysis, a widely used tool for measuring genome-wide gene expression, has been used to explore differential gene expression profiles. A549 cells stimulated with PM2.5 and cigarette smoke extract (CSE) showed elevated GK5 expression in a dose-dependent manner. Transmission electron microscopy and oil red O staining were used to observe LDs in cells. Further, GK5 overexpressing cells showed increased LDs and upregulation of genes and proteins related to lipogenesis and lipid transportation. Affymetrix microarray analysis revealed that GK5 overexpression resulted in the differential expression of more than 109 genes, which were mainly involved in the regulation of cell death, cell survival, cellular movement and migration, and those involved in cellular growth and proliferation pathways. Overall, this study demonstrates that GK5 is upregulated during PM2.5 and cigarette smoke exposure and induces LD synthesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1440-1681.13463DOI Listing
April 2021

Solid-phase microextraction integrated nanobiosensors for the serial detection of cytoplasmic dopamine in a single living cell.

Biosens Bioelectron 2021 Mar 28;175:112915. Epub 2020 Dec 28.

Center Excellence for Environmental Safety and Biological Effects, Beijing Key Laboratory for Green Catalysis and Separation, Department of Chemistry and Biology, Beijing University of Technology, Beijing, China. Electronic address:

Dopamine participates in many physiological and pathological processes. Dynamic monitoring of dopamine levels in the cytoplasm of a single living cell reflects not only the functional state of dopamine synthesis factors but also the processes of related neurodegenerative diseases. Due to the low content of cytoplasmic dopamine and the difficulty to keep cells alive during the operating process, the detection of cytoplasmic dopamine is still challenging. Herein, a solid-phase microextraction (SPME) technique integrated nanobiosensor was employed to trace and quantify dopamine concentration fluctuations in the cytoplasm of a single living cell. We designed a polypyrrole modified carbon fiber nanoprobe as a bifunctional nanoprobe that can extract cytoplasmic dopamine and then perform electrochemical detection. This bifunctional nanoprobe can detect 10 pmol/L extracted dopamine and detected a 60% decrease of the cytoplasmic dopamine concentration in a single living cell by K stimulation. This study allowed for the first time serially detecting cytoplasmic dopamine while keeping the target cell alive, which might yield a new method for research on dopamine neurotoxicity and the related drug action mechanisms for neurodegenerative disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bios.2020.112915DOI Listing
March 2021

Critical role of mTOR in regulating aerobic glycolysis in carcinogenesis (Review).

Int J Oncol 2021 01 25;58(1):9-19. Epub 2020 Nov 25.

Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China.

Mammalian target of rapamycin (mTOR) serves an important role in regulating various biological processes, including cell proliferation, metabolism, apoptosis and autophagy. Among these processes, energy metabolism is the dominant process. The metabolism of not only amino acids, fatty acids and lipids, but also that of nucleotides and glucose has been indicated to be regulated by mTOR. Aerobic glycolysis, which is a specific form of glucose metabolism, is prevalent in carcinomas, and it has been considered to be a potential target for cancer therapy. In reviewing the complexity of the mTOR pathway, it is important to elucidate the central role and detailed pathway via which mTOR regulates glycolysis. In the present study, the complex mechanisms via which mTOR regulates aerobic glycolysis were comprehensively reviewed to highlight the potential of drug development via targeting the molecules associated with mTOR and glycolysis and to further provide strategies for the clinical treatment of cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ijo.2020.5152DOI Listing
January 2021