Publications by authors named "Le Tang"

55 Publications

Potassium Channel Protein KCNK6 Promotes Breast Cancer Cell Proliferation, Invasion, and Migration.

Front Cell Dev Biol 2021 14;9:616784. Epub 2021 Jun 14.

NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.

Breast cancer is the most common malignant tumor in women, and its incidence is increasing each year. To effectively treat breast cancer, it is important to identify genes involved in its occurrence and development and to exploit them as potential drug therapy targets. Here, we found that potassium channel subfamily K member 6 (KCNK6) is significantly overexpressed in breast cancer, however, its function in tumors has not been reported. We further verified that KCNK6 expression is upregulated in breast cancer biopsies. Moreover, overexpressed KCNK6 was found to enhance the proliferation, invasion, and migration ability of breast cancer cells. These effects may occur by weakening cell adhesion and reducing cell hardness, thus affecting the malignant phenotype of breast cancer cells. Our study confirmed, for the first time, that increased KCNK6 expression in breast cancer cells may promote their proliferation, invasion, and migration. Moreover, considering that ion channels serve as therapeutic targets for many small molecular drugs in clinical treatment, targeting KCNK6 may represent a novel strategy for breast cancer therapies. Hence, the results of this study provide a theoretical basis for KCNK6 to become a potential molecular target for breast cancer treatment in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2021.616784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237943PMC
June 2021

Combined Treatment of Cinobufotalin and Gefitinib Exhibits Potent Efficacy against Lung Cancer.

Evid Based Complement Alternat Med 2021 20;2021:6612365. Epub 2021 Mar 20.

Department of Respiratory Neurology, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi 830000, China.

This study aimed to evaluate the efficacy of cinobufotalin combined with gefitinib in the treatment of lung cancer. A549 cells were treated with gefitinib, cinobufotalin, or cinobufotalin plus gefitinib. MTT assay, annexin-V/PI staining and flow cytometry, TUNEL staining, DCFH-DA staining, Western blot, and real-time RT-PCR were performed to investigate the synergistic inhibitory effect of cinobufotalin combined with gefitinib on the growth of A549 cells. Results showed that cinobufotalin synergized with gefitinib displayed inhibited cell viability and enhanced apoptosis in the combination group. Cinobufotalin combined with gefitinib induced a significant enhancement in reactive oxygen species (ROS) production accompanied by cell cycle arrest in the S phase arrest, characterized by upregulation of p21 and downregulation of cyclin A, cyclin E, and CDK2. Besides, cinobufotalin plus gefitinib downregulated the levels of HGF and c-Met. In summary, cinobufotalin combined with gefitinib impedes viability and facilitates apoptosis of A549 cells, indicating that the combined therapy might be a new promising treatment for lung cancer patients who are resistant to gefitinib.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/6612365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189783PMC
March 2021

Advanced Application of Raman Spectroscopy and Surface-Enhanced Raman Spectroscopy in Plant Disease Diagnostics: A Review.

J Agric Food Chem 2021 Mar 8;69(10):2950-2964. Epub 2021 Mar 8.

College of Information Engineering, Suzhou University, 1769 Xuefu Avenue, Suzhou, People's Republic of China.

Plant diseases result in 20-40% of agricultural loss every year worldwide. Timely detection of plant diseases can effectively prevent the development and spread of diseases and ensure the agricultural yield. High-throughput and rapid methods are in great demand. This review investigates the advanced application of Raman spectroscopy (RS) and surface-enhanced Raman spectroscopy (SERS) in the detection of plant diseases. The determination of bacterial diseases and stress-induced diseases, fungal diseases, viral diseases, pests in beans, and mycotoxins related to plant diseases using RS and SERS are discussed in detail. Then, biomarkers for RS and SERS detection are analyzed with regard to plant disease diagnosis. Finally, the advantages and challenges are further illustrated. Additionally, potential alternatives are proposed for the challenges. The review is expected to provide a reference and guidance for the use of RS and SERS in plant disease diagnostics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jafc.0c07205DOI Listing
March 2021

Single-cell RNA sequencing in cancer research.

J Exp Clin Cancer Res 2021 Mar 1;40(1):81. Epub 2021 Mar 1.

NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, The Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Cancer Hospital, Central South University, Changsha, Hunan, China.

Single-cell RNA sequencing (scRNA-seq), a technology that analyzes transcriptomes of complex tissues at single-cell levels, can identify differential gene expression and epigenetic factors caused by mutations in unicellular genomes, as well as new cell-specific markers and cell types. scRNA-seq plays an important role in various aspects of tumor research. It reveals the heterogeneity of tumor cells and monitors the progress of tumor development, thereby preventing further cellular deterioration. Furthermore, the transcriptome analysis of immune cells in tumor tissue can be used to classify immune cells, their immune escape mechanisms and drug resistance mechanisms, and to develop effective clinical targeted therapies combined with immunotherapy. Moreover, this method enables the study of intercellular communication and the interaction of tumor cells and non-malignant cells to reveal their role in carcinogenesis. scRNA-seq provides new technical means for further development of tumor research and is expected to make significant breakthroughs in this field. This review focuses on the principles of scRNA-seq, with an emphasis on the application of scRNA-seq in tumor heterogeneity, pathogenesis, and treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13046-021-01874-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919320PMC
March 2021

circSETD3 regulates MAPRE1 through miR-615-5p and miR-1538 sponges to promote migration and invasion in nasopharyngeal carcinoma.

Oncogene 2021 01 29;40(2):307-321. Epub 2020 Oct 29.

NHC Key Laboratory of Carcinogenesis, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.

Circular RNAs (circRNAs) play an essential role in tumorigenesis and development. However, they have rarely been investigated in nasopharyngeal carcinoma (NPC). This study aimed to investigate the role of circRNA in the invasion and metastasis of NPC. We screened and verified the high expression of circSETD3 in NPC cell lines using RNA sequencing (RNA-Seq) and verified the results of NPC biopsy samples using real-time quantitative polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH). In vivo and in vitro experiments indicated that circSETD3 could promote NPC cell invasion and migration. We compared the proteomic data of NPC cells before and after the overexpression or knockdown of circSETD3 in combination with bioinformatics prediction and experimental verification. It was found that circSETD3 competitively adsorbs to miR-615-5p and miR-1538 and negates their inhibitory effect on MAPRE1 mRNA, thereby upregulating the expression of MAPRE1. The upregulated MAPRE1 then inhibits the acetylation of α-tubulin, promotes the dynamic assembly of microtubules, and enhances the invasion and migration capabilities of NPC cells. The results of this study suggest that circSETD3 is a novel molecular marker and a potential target for NPC diagnosis and treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41388-020-01531-5DOI Listing
January 2021

Employee Political Skill, Supervisor-Subordinate Guanxi, and Work-Family Conflict: The Cross-Level Moderating Role of Family-Friendly Practices.

Int J Environ Res Public Health 2020 07 17;17(14). Epub 2020 Jul 17.

Periodical Head Office, Capital University of Economics and Business, Beijing 100026, China.

Many studies have examined the negative effects of work-family conflict on society, organizations, and individuals. Nonetheless, alleviating employee work-family conflict is a topic worthy of further investigation. Few studies examine the antecedent variables of work-family conflict from personal skill and Guanxi perspectives. Studies that test the moderating role of family-friendly practices at the organization level are also rare. Accordingly, we collected data from 404 employees of 51 organizations. The research data are time-lagged and multileveled. The results of hierarchical linear model (HLM) show: (1) Employee political skill negatively affects employee perceived work-family conflict; (2) Employee political skill positively affects supervisor-subordinate Guanxi; (3) Supervisor-subordinate Guanxi partially mediates the relationship between employee political skill and employee work-family conflict (that is, employees can use their political skill to build high-quality supervisor-subordinate Guanxi, further reducing their perceived work-family conflict); (4) Organization family-friendly practices negatively moderate the relationship between supervisor-subordinate Guanxi and work-family conflict (that is, in organizations with high level family-friendly practices, the negative relationship between supervisor-subordinate Guanxi and work-family conflict becomes weak); Furthermore, by coding with Mplus software (Muthen & Muthen, Los Angeles, CA, USA), we also find: (5) Organization family-friendly practices moderate the indirect effect of employee political skill on employee work-family conflict. The results have both theoretical and empirical implications. Further research directions are addressed at the end.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph17145185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399974PMC
July 2020

Metabolic crosstalk in the tumor microenvironment regulates antitumor immunosuppression and immunotherapy resisitance.

Cell Mol Life Sci 2021 Jan 11;78(1):173-193. Epub 2020 Jul 11.

Department of Stomatology, NHC Key Laboratory of Carcinogenesis, Xiangya Hospital, Central South University, Changsha, 410078, China.

The successful treatment of human cancers by immunotherapy has been made possible by breakthroughs in the discovery of immune checkpoint regulators, including CTLA-4 and PD-1/PD-L1. However, the immunosuppressive effect of the tumor microenvironment still represents an important bottleneck that limits the success of immunotherapeutic approaches. The tumor microenvironment influences the metabolic crosstalk between tumor cells and tumor-infiltrating immune cells, creating competition for the utilization of nutrients and promoting immunosuppression. In addition, tumor-derived metabolites regulate the activation and effector function of immune cells through a variety of mechanisms; in turn, the metabolites and other factors secreted by immune cells can also become accomplices to cancer development. Immune-metabolic checkpoint regulation is an emerging concept that is being studied with the aim of restoring the immune response in the tumor microenvironment. In this review, we summarize the metabolic reprogramming of various cell types present in the tumor microenvironment, with a focus on the interaction between the metabolic pathways of these cells and antitumor immunosuppression. We also discuss the main metabolic checkpoints that could provide new means of enhancing antitumor immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00018-020-03581-0DOI Listing
January 2021

Epstein-Barr virus-encoded miR-BART6-3p inhibits cancer cell proliferation through the LOC553103-STMN1 axis.

FASEB J 2020 06 18;34(6):8012-8027. Epub 2020 Apr 18.

NHC Key Laboratory of Carcinogenesis, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.

Epstein-Barr virus (EBV) is a tumorigenic virus that can cause various human malignancies such as nasopharyngeal carcinoma (NPC) and gastric cancer (GC). EBV encodes 44 mature micro (mi)RNAs, mostly exhibiting oncogenic properties and promoting cancer progression. However, we have previously found that one EBV-encoded miRNA, namely EBV-miR-BART6-3p, acts as a tumor suppressor by inhibiting metastasis and invasion. Here, we report that EBV-miR-BART6-3p inhibits the proliferation of EBV-associated cancers, NPC, and GC, by targeting and downregulating a long non-coding RNA (lncRNA), LOC553103. Through proteomics analysis, we determined that stathmin (STMN1) is affected by EBV-miR-BART6-3p and LOC553103. Further, via RNA immunoprecipitation and luciferase reporter assay, we confirmed that LOC553103 directly binds and stabilizes the 3'UTR region of STMN1 mRNA. These results indicate that the EBV-miR-BART6-3p/LOC553103/STMN1 axis regulates the expression of cell cycle-associated proteins, which then inhibit EBV-associated tumor cell proliferation. These findings provide potential targets or strategies for novel EBV-related cancer treatments, as well as contributes new insights into the understanding of EBV infection-related carcinogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1096/fj.202000039RRDOI Listing
June 2020

E. coli diversity: low in colorectal cancer.

BMC Med Genomics 2020 04 6;13(1):59. Epub 2020 Apr 6.

Systemomics Center, College of Pharmacy, and Genomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, 157 Baojian Road, Harbin, 150081, China.

Background: Escherichia coli are mostly commensals but also contain pathogenic lineages. It is largely unclear whether the commensal E. coli as the potential origins of pathogenic lineages may consist of monophyletic or polyphyletic populations, elucidation of which is expected to lead to novel insights into the associations of E. coli diversity with human health and diseases.

Methods: Using genomic sequencing and pulsed field gel electrophoresis (PFGE) techniques, we analyzed E. coli from the intestinal microbiota of three groups of healthy individuals, including preschool children, university students, and seniors of a longevity village, as well as colorectal cancer (CRC) patients, to probe the commensal E. coli populations for their diversity.

Results: We delineated the 2280 fresh E. coli isolates from 185 subjects into distinct genome types (genotypes) by PFGE. The genomic diversity of the sampled E. coli populations was so high that a given subject may have multiple genotypes of E. coli, with the general diversity within a host going up from preschool children through university students to seniors. Compared to the healthy subjects, the CRC patients had the lowest diversity level among their E. coli isolates. Notably, E. coli isolates from CRC patients could suppress the growth of E. coli bacteria isolated from healthy controls under nutrient-limited culture conditions.

Conclusions: The coexistence of multiple E. coli lineages in a host may help create and maintain a microbial environment that is beneficial to the host. As such, the low diversity of E. coli bacteria may be associated with unhealthy microenvironment in the intestine and hence facilitate the pathogenesis of diseases such as CRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12920-020-0704-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7133007PMC
April 2020

Abnormal X chromosome inactivation and tumor development.

Cell Mol Life Sci 2020 Aug 10;77(15):2949-2958. Epub 2020 Feb 10.

Department of Stomatology, NHC Key Laboratory of Carcinogenesis, Xiangya Hospital, Central South University, Changsha, Hunan, China.

During embryonic development, one of the two X chromosomes of a mammalian female cell is randomly inactivated by the X chromosome inactivation mechanism, which is mainly dependent on the regulation of the non-coding RNA X-inactive specific transcript at the X chromosome inactivation center. There are three proteins that are essential for X-inactive specific transcript to function properly: scaffold attachment factor-A, lamin B receptor, and SMRT- and HDAC-associated repressor protein. In addition, the absence of X-inactive specific transcript expression promotes tumor development. During the process of chromosome inactivation, some tumor suppressor genes escape inactivation of the X chromosome and thereby continue to play a role in tumor suppression. A well-functioning tumor suppressor gene on the idle X chromosome in women is one of the reasons they have a lower propensity to develop cancer than men, women thereby benefit from this enhanced tumor suppression. This review will explore the mechanism of X chromosome inactivation, discuss the relationship between X chromosome inactivation and tumorigenesis, and consider the consequent sex differences in cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00018-020-03469-zDOI Listing
August 2020

Genetic boundaries delineate the potential human pathogen Salmonella bongori into discrete lineages: divergence and speciation.

BMC Genomics 2019 Dec 4;20(1):930. Epub 2019 Dec 4.

Systemomics Center, College of Pharmacy, and Genomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, 157 Baojian Road, Harbin, 150081, China.

Background: Salmonella bongori infect mainly cold-blooded hosts, but infections by S. bongori in warm-blooded hosts have been reported. We hypothesized that S. bongori might have diverged into distinct phylogenetic lineages, with some being able to infect warm-blooded hosts.

Results: To inspect the divergence status of S. bongori, we first completely sequenced the parakeet isolate RKS3044 and compared it with other sequenced S. bongori strains. We found that RKS3044 contained a novel T6SS encoded in a pathogenicity island-like structure, in addition to a T6SS encoded in SPI-22, which is common to all S. bongori strains so far reported. This novel T6SS resembled the SPI-19 T6SS of the warm-blooded host infecting Salmonella Subgroup I lineages. Genomic sequence comparisons revealed different genomic sequence amelioration events among the S. bongori strains, including a unique CTAG tetranucleotide degeneration pattern in RKS3044, suggesting non-overlapping gene pools between RKS3044 and other S. bongori lineages/strains leading to their independent accumulation of genomic variations. We further proved the existence of a clear-cut genetic boundary between RKS3044 and the other S. bongori lineages/strains analyzed in this study.

Conclusions: The warm-blooded host-infecting S. bongori strain RKS3044 has diverged with distinct genomic features from other S. bongori strains, including a novel T6SS encoded in a previously not reported pathogenicity island-like structure and a unique genomic sequence degeneration pattern. These findings alert cautions about the emergence of new pathogens originating from non-pathogenic ancestors by acquiring specific pathogenic traits.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12864-019-6259-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894293PMC
December 2019

Effects and Molecular Mechanism of L-Type Calcium Channel on Fluoride-Induced Kidney Injury.

Biol Trace Elem Res 2020 Sep 2;197(1):213-223. Epub 2019 Dec 2.

College of Xing Zhi, Zhejiang Normal University, Jinhua, Zhejiang, 321004, People's Republic of China.

This study aimed to investigate the role and molecular mechanism of L-type calcium channel (LTCC) on fluoride exposure-induced kidney injury. Subchronic and chronic fluoride exposures were included in the experiment. Each part contained 140 ICR male mice. They were randomly divided into 7 groups: control group, high-fluoride group (NaF 30 mg/L), low-fluoride group (NaF 5 mg/L), high/low-fluoride + agonist (FPL64176) group, high/low-fluoride + inhibitor (nifedipine) group. One week before the end of fluoride exposure, each mouse in the fluoride exposure group was injected intraperitoneally with LTCC agonist (FPL64176) or inhibitor (nifedipine) (5 mg/kg day). The apoptosis of kidney cell was observed by TUNEL, and the protein expression levels of Cav1.2 and CaM, CaMKII, Bcl-2, and Bax were detected by Western blot. Compared with the control group, the protein expression levels of Cav1.2, CaM, and Bax significantly increased, and those of CaMKII and Bcl-2 significantly decreased, the ratio of Bax/Bcl-2 also significantly increased, and the number of apoptotic kidney cells significantly increased in the high/low-fluoride group and in the high/low-fluoride + agonist group. The above indicators and fluoride exposure concentrations showed in time- and dose-dependent changes. Compared with the high/low-fluoride + agonist group, the protein expression level of the molecular in the kidney cells above mentioned was significantly opposite and the number of apoptotic kidney cells significantly decreased in the high/low-fluoride + inhibitor group. In conclusion, LTCC mediates the kidney injury induced by fluoride exposure in mice. Fluoride exposure induced abnormal expression of the Cav1.2 protein, Ca signal transduction pathway, and apoptosis-regulated proteins, which is one of the molecular mechanisms. Nifedipine may be a new and effective anti-fluoride drug.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12011-019-01987-xDOI Listing
September 2020

Herpesvirus acts with the cytoskeleton and promotes cancer progression.

J Cancer 2019 21;10(10):2185-2193. Epub 2019 May 21.

NHC Key Laboratory of Carcinogenesis, Xiangya Hospital, Central South University, Changsha, Hunan, China.

The cytoskeleton is a complex fibrous reticular structure composed of microfilaments, microtubules and intermediate filaments. These components coordinate morphology support and intracellular transport that is involved in a variety of cell activities, such as cell proliferation, migration and differentiation. In addition, the cytoskeleton also plays an important role in viral infection. During an infection by a Herpesvirus, the virus utilizes microfilaments to enter cells and travel to the nucleus by microtubules; the viral DNA replicates with the help of host microfilaments; and the virus particles start assembling with a capsid in the cytoplasm before egress. The cytoskeleton changes in cells infected with Herpesvirus are made to either counteract or obey the virus, thereby promote cell transforming into cancerous ones. This article aims to clarify the interaction between the virus and cytoskeleton components in the process of Herpesvirus infection and the molecular motor, cytoskeleton-associated proteins and drugs that play an important role in the process of a Herpesvirus infection and carcinogenesis process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/jca.30222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584404PMC
May 2019

Evaluating stress, satisfaction and the associated influencing factors of participants in cancer clinical trials: a cross-sectional study in China.

BMJ Open 2019 06 1;9(5):e028589. Epub 2019 Jun 1.

Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Objectives: Patients' stress and satisfaction concerning cancer clinical trials (CCT) may affect study accrual and quality. Our study aimed to evaluate stress and satisfaction in CCT and the influencing factors.

Design: Cross-sectional analysis done by a questionnaire after informed consent.

Setting: Cancer Hospital, Chinese Academy of Medical Sciences.

Participants: 199 CCT participants. Primary and secondary outcome measures self-assessed stress and satisfaction in CCT.

Results: Among 199 participants, 83.9% would join CCT again; 72.9% had enough time to decide on trial participation; 73.9% claimed complete awareness of CCT; 3.5% doubted CCT's significance and scientific quality; 33.2% deemed CCT time-consuming; 73.9% scored satisfaction ≥9/10; and 25.6% claimed moderate to severe stress. Positive factors for satisfaction were enough decision time (OR=0.36, p=0.0003), better impressions of doctors (OR=0.41, p=0.047) and less time-consuming trials (OR=0.43, p<0.0001). Individuals with more prior uninsured medical expenses (OR=1.23, p=0.026), less time consumption (OR=2.35, p<0.0001) and more tests in CCT (OR=0.64, p=0.035) were less likely to experience stress. Phase III study participants bore less stress than phase II (OR=0.29, p=0.032) but more than phase I (OR=1.18, p=0.009).

Conclusions: Our study addressed factors influencing CCT participants' stress and satisfaction. We suggested measures to improve patients' experiences in CCT.

Trial Registration Number: NCT03412344; Pre-results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2018-028589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549607PMC
June 2019

Cloning and characterization of the putative AFAP1-AS1 promoter region.

J Cancer 2019 29;10(5):1145-1153. Epub 2019 Jan 29.

NHC Key Laboratory of Carcinogenesis, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Actin filament-associated protein 1-antisense RNA1 (AFAP1-AS1), a cancer-related long non-coding RNA, has been found to be upregulated in multiple types of cancers. AFAP1-AS1 is important for the initiation, progression and poor prognosis of many cancers, including nasopharyngeal carcinoma (NPC). However, the mechanism underlying the regulation of AFAP1-AS1 expression is not well-understood. In our study, the potential promoter region of AFAP1-AS1 was predicted by comprehensive bioinformatics analysis. Moreover, promoter deletion analysis identified the sequence between positions -359 and -28 bp as the minimal promoter region of AFAP1-AS1. The ChIP assay results indicate that the AFAP1-AS1 promoter is responsive to the transcription factor c-Myc, which can promote high AFAP1-AS1 expression. This study is the first to clone and characterize the AFAP1-AS1 promoter region. Our findings will help to better understand the underlying mechanism of high AFAP1-AS1 expression in tumorigenesis and to develop new strategies for therapeutic high expression of AFAP1-AS1 in NPC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/jca.29049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400686PMC
January 2019

Tranylcypromine and 6-trifluoroethyl thienopyrimidine hybrid as LSD1 inhibitor.

Bioorg Med Chem Lett 2019 03 18;29(6):844-847. Epub 2019 Jan 18.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, PR China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, PR China. Electronic address:

Tranylcypromine moiety extracted from LSD1 inhibitors and 6-trifluoroethyl thienopyrimidine moiety from menin-MLL1 PPI inhibitors were merged to give new chemotypes for medicinal chemistry study. Among 15 new compounds prepared in this work, some exhibited nanomolar LSD1 activity and good selectivity over MAO-A/B, low micromolar menin-MLL1 PPI inhibitory activity, as well as submicromolar MV4-11 antiprofilative activities. Intracellular LSD1 engagement of compounds with higher enzymatic and antiproliferative activities was confirmed by CD86 mRNA up-regulation experiments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmcl.2019.01.017DOI Listing
March 2019

Distinct evolutionary origins of common multi-drug resistance phenotypes in Salmonella typhimurium DT104: a convergent process for adaptation under stress.

Mol Genet Genomics 2019 Jun 1;294(3):597-605. Epub 2019 Feb 1.

Systemomics Center, College of Pharmacy, and Genomics Research Center, Harbin Medical University, 157 Baojian Road, Harbin, 150081, China.

Antimicrobial resistance makes pathogenic bacteria hard to control, but little is known about the general processes of resistance gain or loss. Here, we compared distinct S. typhimurium DT104 strains resistant to zero, two, five, or more of the tested antimicrobials. We found that common resistance phenotypes could be encoded by distinct genes, on SGI-1 or plasmid. We also demonstrated close clonality among all the tested non-resistant and differently resistant DT104 strains, demonstrating dynamic acquisition or loss (by total deletion or gradual decaying of multi-drug resistance gene clusters) of the genetic traits. These findings reflect convergent processes to make the bacteria resistant to multiple antimicrobials by acquiring the needed traits from stochastically available origins. When the antimicrobial stress is absent, the resistance genes may be dropped off quickly, so the bacteria can save the cost for maintaining unneeded genes. Therefore, this work reiterates the importance of strictly controlled use of antimicrobials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00438-019-01531-5DOI Listing
June 2019

An abbreviated version of Silhouettes test: a brief validated mild cognitive impairment screening tool.

Int Psychogeriatr 2018 Dec 19:1-8. Epub 2018 Dec 19.

Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College,Fudan University, Shanghai,China.

ABSTRACTObjectives:To revise an abbreviated version of the Silhouettes subtest of the Visual Object and Space Perception (VOSP) battery in order to recognize mild cognitive impairment (MCI) and determine the optimal cutoffs to differentiate among cognitively normal controls (NC), MCI, and Alzheimer's Disease (AD) in the Chinese elderly.

Design: A cross-sectional validation study.

Setting: Huashan Hospital, Shanghai, China.

Subjects: A total of 591 participants: Individuals with MCI (n = 211), AD (n = 139) and NC (n = 241) were recruited from the Memory Clinic, Huashan Hospital, Shanghai, China.

Methods: Baseline neuropsychological battery (including VOSP) scores were collected from firsthand data. An abbreviated version of silhouettes test (Silhouettes-A) was revised from the original English version more suitable for the elderly, including eight silhouettes of animals and seven silhouettes of inanimate objects, with a score ranging from 0 to 15.

Results: Silhouettes-A was an effective test to screen MCI in the Chinese elderly with good sensitivity and specificity, similar to the Montreal cognitive assessment and superior to other single tests reflecting language, spatial, or executive function. However, it had no advantage in distinguishing MCI from AD. The corresponding optimal cutoff scores of Silhouettes-A were 10 for screening MCI and 8 for AD.

Conclusion: Silhouettes-A is a quick, simple, sensitive, and dependable cognitive test to distinguish among NC, MCI, and AD patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1041610218001230DOI Listing
December 2018

Effects of tumor metabolic microenvironment on regulatory T cells.

Mol Cancer 2018 11 26;17(1):168. Epub 2018 Nov 26.

The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China.

Recent studies have shown that on one hand, tumors need to obtain a sufficient energy supply, and on the other hand they must evade the body's immune surveillance. Because of their metabolic reprogramming characteristics, tumors can modify the physicochemical properties of the microenvironment, which in turn affects the biological characteristics of the cells infiltrating them. Regulatory T cells (Tregs) are a subset of T cells that regulate immune responses in the body. They exist in large quantities in the tumor microenvironment and exert immunosuppressive effects. The main effect of tumor microenvironment on Tregs is to promote their differentiation, proliferation, secretion of immunosuppressive factors, and chemotactic recruitment to play a role in immunosuppression in tumor tissues. This review focuses on cell metabolism reprogramming and the most significant features of the tumor microenvironment relative to the functional effects on Tregs, highlighting our understanding of the mechanisms of tumor immune evasion and providing new directions for tumor immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12943-018-0913-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260778PMC
November 2018

Vibrio parahaemolyticus RhsP represents a widespread group of pro-effectors for type VI secretion systems.

Nat Commun 2018 09 25;9(1):3899. Epub 2018 Sep 25.

Faculty of Health Sciences, University of Macau, Macau SAR, China.

Type VI secretion systems (T6SSs) translocate effector proteins, such as Rhs toxins, to eukaryotic cells or prokaryotic competitors. All T6SS Rhs-type effectors characterized thus far contain a PAAR motif or a similar structure. Here, we describe a T6SS-dependent delivery mechanism for a subset of Rhs proteins that lack a PAAR motif. We show that the N-terminal Rhs domain of protein RhsP (or VP1517) from Vibrio parahaemolyticus inhibits the activity of the C-terminal DNase domain. Upon auto-proteolysis, the Rhs fragment remains inside the cells, and the C-terminal region interacts with PAAR2 and is secreted by T6SS2; therefore, RhsP acts as a pro-effector. Furthermore, we show that RhsP contributes to the control of certain "social cheaters" (opaR mutants). Genes encoding proteins with similar Rhs and PAAR-interacting domains, but diverse C-terminal regions, are widely distributed among Vibrio species.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-018-06201-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156420PMC
September 2018

Chinese version of Montreal Cognitive Assessment Basic for discrimination among different severities of Alzheimer's disease.

Neuropsychiatr Dis Treat 2018 21;14:2133-2140. Epub 2018 Aug 21.

Department of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China,

Objectives: To find out whether the Chinese version of Montreal Cognitive Assessment Basic (MoCA-BC) and its subtests could be applied in discrimination among cognitively normal controls (NC), mild cognitive impairment (MCI), mild and moderate Alzheimer's Disease (AD), and furthermore, to determine the optimal cutoffs most sensitive to distinguish between them.

Design: A cross-sectional validation study.

Setting: Huashan Hospital, Shanghai, China.

Participants: There was a total of 1,969 participants: individuals with MCI (n=663), mild (n=345), moderate (n=441) AD, and cognitively NC (n=520) were recruited from the Memory Clinic, Huashan Hospital, Shanghai, China.

Measurements: Baseline MoCA-BC scores were collected from firsthand data. Two subtests were calculated from MoCA-BC: the Memory Index Score of MoCA-BC (MoCA-BC-MIS) and the Non-memory Index Score of MoCA-BC (MoCA-BC-NM).

Results: MoCA-BC was an effective cognitive tool to discriminate among NC, MCI, mild and moderate AD in the Chinese elderly across all education groups, implying that it was efficient not only for detecting MCI, but for different severities of AD as well. For MCI screening, the total score of MoCA-BC (MoCA-BC-T) and MoCA-BC-MIS had similar high sensitivity and specificity. For discrimination among MCI, mild and moderate AD, the MoCA-BC-T and MoCA-BC-NM had similar performance.

Conclusion: MoCA-BC is an effective cognitive test to distinguish between NC, MCI, mild and moderate AD among the Chinese elderly with various levels of education.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/NDT.S174293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6110265PMC
August 2018

The neuropsychological profiles and semantic-critical regions of right semantic dementia.

Neuroimage Clin 2018 29;19:767-774. Epub 2018 May 29.

Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China. Electronic address:

Introduction: Previous literature has revealed that the anterior temporal lobe (ATL) is the semantic hub of left-sided or mixed semantic dementia (SD), whilst the semantic hub of right-sided SD has not been examined.

Methods: Seventeen patients with right-sided SD, 18 patients with left-sided SD and 20 normal controls (NC) underwent neuropsychological assessments and magnetic resonance imaging scans. We investigated the relationship between the degree of cerebral atrophy in the whole brain and the severity of semantic deficits in left and right-sided SD samples, respectively.

Results: We found the semantic deficits of right-sided SD patients were related to bilateral fusiform gyri and left temporal pole, whilst the left fusiform gyrus correlated with the semantic performance of left-sided SD patients. Moreover, all the findings couldn't be accounted for by total gray matter volume (GMV) or general cognitive degradation of patients.

Discussion: These results provide novel evidence for the current semantic theory, that the important regions for semantic processing include both anterior and posterior temporal lobes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nicl.2018.05.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6041419PMC
January 2019

Role of metabolism in cancer cell radioresistance and radiosensitization methods.

J Exp Clin Cancer Res 2018 Apr 23;37(1):87. Epub 2018 Apr 23.

The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Background: Radioresistance is a major factor leading to the failure of radiotherapy and poor prognosis in tumor patients. Following the application of radiotherapy, the activity of various metabolic pathways considerably changes, which may result in the development of resistance to radiation.

Main Body: Here, we discussed the relationships between radioresistance and mitochondrial and glucose metabolic pathways, aiming to elucidate the interplay between the tumor cell metabolism and radiotherapy resistance. In this review, we additionally summarized the potential therapeutic targets in the metabolic pathways.

Short Conclusion: The aim of this review was to provide a theoretical basis and relevant references, which may lead to the improvement of the sensitivity of radiotherapy and prolong the survival of cancer patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13046-018-0758-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5914062PMC
April 2018

BPIFB1 (LPLUNC1) inhibits radioresistance in nasopharyngeal carcinoma by inhibiting VTN expression.

Cell Death Dis 2018 04 1;9(4):432. Epub 2018 Apr 1.

The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Bactericidal/permeability-increasing-fold-containing family B member 1 (BPIFB1, previously named LPLUNC1) is highly expressed in the nasopharynx and significantly downregulated in nasopharyngeal carcinoma (NPC). Low expression is also associated with poor prognosis in patients with NPC. Radiotherapy is a routine treatment for NPC; however, radioresistance is a major cause of treatment failure. Thus, we aimed to investigate the role of BPIFB1 in the radioresponse of NPC. Colony formation and cell survival results showed that BPIFB1 sensitized NPC cells to ionizing radiation. VTN, a previously identified BPIFB1-binding protein, was shown to induce cell proliferation and survival, G2/M phase arrest, DNA repair, activation of the ATM-Chk2 and ATR-Chk1 pathways, and anti-apoptotic effects after exposure to radiation, facilitating NPC cell radioresistance. However, BPIFB1 inhibited this VTN-mediated radioresistance, ultimately improving NPC radiosensitivity. In conclusion, this study is the first to demonstrate the functions of BPIFB1 and VTN in the NPC radioresponse. Our findings indicated that promoting BPIFB1 expression and targeting VTN might represent new therapeutic strategies for NPC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-018-0409-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5864881PMC
April 2018

A phase I study of different doses and frequencies of pegylated recombinant human granulocyte-colony stimulating factor (PEG rhG-CSF) in patients with standard-dose chemotherapy-induced neutropenia.

Chin J Cancer Res 2017 Oct;29(5):402-410

Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China These authors contributed equally to this work.

Objective: The recommended dose of prophylactic pegylated recombinant human granulocyte-colony stimulating factor (PEG rhG-CSF) is 100 μg/kg once per cycle for patients receiving intense-dose chemotherapy. However, few data are available on the proper dose for patients receiving less-intense chemotherapy. The aim of this phase I study is to explore the proper dose and administration schedule of PEG rhG-CSF for patients receiving standard-dose chemotherapy.

Methods: Eligible patients received 3-cycle chemotherapy every 3 weeks. No PEG rhG-CSF was given in the first cycle. Patients experienced grade 3 or 4 neutropenia would then enter the cycle 2 and 3. In cycle 2, patients received a single subcutaneous injection of prophylactic PEG rhG-CSF on d 3, and received half-dose subcutaneous injection in cycle 3 on d 3 and d 5, respectively. Escalating doses (30, 60, 100 and 200 μg/kg) of PEG rhG-CSF were investigated.

Results: A total of 26 patients were enrolled and received chemotherapy, in which 24 and 18 patients entered cycle 2 and cycle 3 treatment, respectively. In cycle 2, the incidence of grade 3 or 4 neutropenia for patients receiving single-dose PEG rhG-CSF of 30, 60, 100 and 200 μg/kg was 66.67%, 33.33%, 22.22% and 0, respectively, with a median duration less than 1 (0-2) d. No grade 3 or higher neutropenia was noted in cycle 3 in all dose cohorts.

Conclusions: The pharmacokinetic and pharmacodynamic profiles of PEG rhG-CSF used in cancer patients were similar to those reported, as well as the safety. Double half dose administration model showed better efficacy result than a single dose model in terms of grade 3 neutropenia and above. The single dose of 60 μg/kg, 100 μg/kg and double half dose of 30 μg/kg were recommended to the phase II study, hoping to find a preferable method for neutropenia treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21147/j.issn.1000-9604.2017.05.04DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5675917PMC
October 2017

Trend analysis of cancer incidence and mortality in China.

Sci China Life Sci 2017 11 16;60(11):1271-1275. Epub 2017 Oct 16.

Key Laboratory of Carcinogenesis of Ministry of Health, Xiangya Hospital, Central South University, Changsha, 410078, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11427-017-9172-6DOI Listing
November 2017

BPIFB1 (LPLUNC1) inhibits migration and invasion of nasopharyngeal carcinoma by interacting with VTN and VIM.

Br J Cancer 2018 01 9;118(2):233-247. Epub 2017 Nov 9.

The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Background: Bactericidal/Permeability-increasing-fold-containing family B member 1 (BPIFB1, previously termed LPLUNC1) is highly expressed in the nasopharynx, significantly downregulated in nasopharyngeal carcinoma (NPC), and associated with prognosis in NPC patients. Because metastasis represents the primary cause of NPC-related death, we explored the role of BPIFB1 in NPC migration and invasion.

Methods: The role of BPIFB1 in NPC metastasis was investigated in vitro and in vivo. A co-immunoprecipitation assay coupled with mass spectrometry was used to identify BPIFB1-binding proteins. Additionally, western blotting, immunofluorescence, and immunohistochemistry allowed assessment of the molecular mechanisms associated with BPIFB1-specific metastatic inhibition via vitronectin (VTN) and vimentin (VIM) interactions.

Results: Our results showed that BPIFB1 expression markedly inhibited NPC cell migration, invasion, and lung-metastatic abilities. Additionally, identification of two BPIFB1-interacting proteins, VTN and VIM, showed that BPIFB1 reduced VTN expression and the formation of a VTN-integrin αV complex in NPC cells, leading to inhibition of the FAK/Src/ERK signalling pathway. Moreover, BPIFB1 attenuated NPC cell migration and invasion by inhibiting VTN- or VIM-induced epithelial-mesenchymal transition.

Conclusions: This study represents the first demonstration of BPIFB1 function in NPC migration, invasion, and lung metastasis. Our findings indicate that re-expression of BPIFB1 might represent a useful strategy for preventing and treating NPC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/bjc.2017.385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5785741PMC
January 2018

Differential degeneration of the ACTAGT sequence among Salmonella: a reflection of distinct nucleotide amelioration patterns during bacterial divergence.

Sci Rep 2017 09 8;7(1):10985. Epub 2017 Sep 8.

Systemomics Center, College of Pharmacy, and Genomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, China.

When bacteria diverge, they need to adapt to the new environments, such as new hosts or different tissues of the same host, by accumulating beneficial genomic variations, but a general scenario is unknown due to the lack of appropriate methods. Here we profiled the ACTAGT sequence and its degenerated forms (i.e., hexa-nucleotide sequences with one of the six nucleotides different from ACTAGT) in Salmonella to estimate the nucleotide amelioration processes of bacterial genomes. ACTAGT was mostly located in coding sequences but was also found in several intergenic regions, with its degenerated forms widely scattered throughout the bacterial genomes. We speculated that the distribution of ACTAGT and its degenerated forms might be lineage-specific as a consequence of different selection pressures imposed on ACTAGT at different genomic locations (in genes or intergenic regions) among different Salmonella lineages. To validate this speculation, we modelled the secondary structures of the ACTAGT-containing sequences conserved across Salmonella and many other enteric bacteria. Compared to ACTAGT at conserved regions, the degenerated forms were distributed throughout the bacterial genomes, with the degeneration patterns being highly similar among bacteria of the same phylogenetic lineage but radically different across different lineages. This finding demonstrates biased amelioration under distinct selection pressures among the bacteria and provides insights into genomic evolution during bacterial divergence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-017-11226-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5591236PMC
September 2017

Abnormality of Klotho Signaling Is Involved in Polycystic Ovary Syndrome.

Reprod Sci 2018 03 4;25(3):372-383. Epub 2017 Jul 4.

1 Reproductive Medicine Center, Reproductive Medicine Hospital of Hunan Province, Changsha, Hunan, People's Republic of China.

This study investigated the involvement of the klotho-associated signaling in the apoptosis of granulosa cells (GCs) from the ovaries of patients with polycystic ovary syndrome (PCOS) and PCOS animals. Primary GCs were obtained from 26 healthy women and 43 women with PCOS. The PCOS animal model was established by the injection of dehydroepiandrosterone (DHEA). Klotho protein and associated microRNA expression in human primary GCs and rats' ovarian tissues were measured by Western blot and real-time polymerase chain reaction, respectively. Results showed that significantly lower miR-126-5p and miR-29a-5p microRNA expressions, higher klotho protein expression, lower insulin growth factor 1 (IGF-1R) and Wnt family member 1 (Wnt1) protein expressions, and lower Akt phosphorylation at Ser and Thr residues were observed in the GCs from patients with PCOS and the ovarian tissues of PCOS rats compared to that in GCs from healthy women and ovarian tissues of normal control rats, respectively. Knockdown of klotho gene expression normalized IGF-1R and Wnt1 protein expressions and Akt phosphorylation in GCs from patients with PCOS and the ovarian tissues from PCOS rats; it also blocked the effects of insulin on apoptosis and proliferation in GCs from patients with PCOS and inhibited caspase-3 activity in ovarian tissues of PCOS rats. Knockdown of klotho gene expression increased the pregnancy rate in DHEA-treated female rats and increased the body weight of their newborns through normalizing the ovarian function and decreasing the formation of cystic follicles. In conclusion, the miR-126-5p, miR-29a-5p/klotho/insulin-IGF-1, Wnt, and Akt signal pathway may be involved in the apoptosis of GCs and subsequent development of PCOS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1933719117715129DOI Listing
March 2018