Publications by authors named "Di Tang"

76 Publications

Targeting MEX3A attenuates metastasis of breast cancer via β-catenin signaling pathway inhibition.

Cancer Lett 2021 Aug 21;521:50-63. Epub 2021 Aug 21.

Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China. Electronic address:

Metastasis is the major cause of mortality in patients with breast cancer. Understanding the metastatic mechanism to guide clinical diagnoses and the treatment of breast cancer remains a challenge. We found that the expression of Mex-3 RNA binding family member A (MEX3A) was upregulated significantly and related to tumor grade in breast cancer. The results of in vitro and in vivo studies showed that knockdown of MEX3A inhibited the metastasis and impaired the stemness of breast cancer cells. Furthermore, activation of the β-catenin signaling pathway was discovered as a molecular intermediate of MEX3A-mediated regulation. We also found that ectopic expression of β-catenin restored the migration ability, invasion ability, and CD44/CD24 percentage of MDA-MB-231 and BT549 cells when MEX3A was depleted. In addition, we revealed that MEX3A positively regulated the expression of β-catenin by downregulating Dickkopf WNT signaling pathway inhibitor 1 (DKK1) expression. Therefore, a previously undiscovered role of MEX3A comprising a critical contribution to promoting metastasis and maintaining the stemness of breast cancer via the Wnt/β-catenin pathway was demonstrated in the present study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.canlet.2021.08.022DOI Listing
August 2021

A calcium phosphate drug carrier loading with 5-fluorouracil achieving a synergistic effect for pancreatic cancer therapy.

J Colloid Interface Sci 2021 Jul 20;605:263-273. Epub 2021 Jul 20.

The Seventh Hospital of Sun Yat-sen University, Sun Yat-sen University, Shenzhen 518107, China. Electronic address:

Calcium based biomaterials were widely used for drug delivery application due to their biodegradability, biocompatibility, and high drug loading capacity. Herein, amino-capped polyamidoamine (PAMAM) dendrimer was applied as a macromolecular template to form amino-modified calcium phosphate hollow sphere (CaPO-NH). After loading with 5-fluorouracil (5Fu), this system performed synergistic cancer chemotherapy. In this study, the 5Fu/CaPO-NH particles could be efficiently uptaken by cancer cells, and then decompose into Ca and release 5Fu drug in the cytoplasm; therefore calcium overload and reactive oxygen species (ROS) accumulation were found in PSN1 cells that could induce cell membrane damage and elicit cell apoptosis through a series of biochemical reactions including endoplasmic reticulum stress, lipid peroxidation and mitochondrial apoptosis. In the PSN1 pancreatic cancer xenograft model, the 5Fu/CaPO-NH system performed high tumor inhibition via chemotherapy and calcium overload induced apoptosis. Comparingly, the normal cells and organs were insensitive to this synergistic therapy, which indicated the well biocompatibility of delivery system. Thus, this study provided a promising CaPO-NH drug delivery platform for enhanced 5Fu chemotherapeutic effect.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcis.2021.07.080DOI Listing
July 2021

The relationship between internal migration and the likelihood of high-risk pregnancy: Hukou system and high-risk pregnancies in China.

BMC Pregnancy Childbirth 2021 Jul 15;21(1):509. Epub 2021 Jul 15.

Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College Street, Suite 425, Toronto, ON, M5T 3M6, Canada.

Background: China has one of the world's largest internal migrant populations. The Chinese Hukou system is a unique household registration system that limits internal migrants in their access to basic urban public services, such as public health insurance and social assistance of their host city. In the case of female internal migrants, this may lead to high-risk pregnancies. The objective of this study is to assess the relationship between internal migrant status (Hukou) and the likelihood of high-risk pregnancies that occur in one large municipal-level obstetrics hospital in Shanghai, China.

Methods: Medical records data from the Shanghai First Maternity and Infant Hospital from January 1, 2013, to May 31, 2018, were used to analyze 133,358 live births for Shanghai natives (n = 83,872) and internal migrant women (n = 49,486). A propensity score matching approach was used in conjunction with logistic regression analysis to identify the role of internal migrant status (Hukou) on the likelihood of high-risk pregnancies.

Results: A greater likelihood of high-risk pregnancies were found among internal migrant women who moved from other parts of China to Shanghai. This effect was more obvious for women who gave birth for the first time and internal migrant women who were employed.

Conclusion: The results show the effects of internal migrant status (Hukou) and the elevated likelihood of high-risk pregnancies among internal migrant women relative to their urban counterparts in Shanghai even after accounting for self-selection by employing the propensity score matching method. China's unique Hukou household registration system limits access to public services for internal migrant women and accordingly may account for the elevated likelihood of high-risk pregnancies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12884-021-03958-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283949PMC
July 2021

circPUM1 Activates the PI3K/AKT Signaling Pathway by Sponging to Promote to Promote the Proliferation, Invasion and Glycolysis of Pancreatic Cancer.

Curr Pharm Biotechnol 2021 Jul 13. Epub 2021 Jul 13.

Department of General Surgery, The Seventh Affiliated Hospital, Sen Yat-sen University, ShenZhen, Guangdong 518017, China.

Background: Our study seeks to obtain data to assess the impacts of circPUM1 on pancreatic cancer (PC) and its mechanism.

Methods: The expression of circPUM1 and miR-200c-3p in PC and normal tissues and PC cell lines was collected and detected. Subsequently, dual-luciferase assay-based verification of the binding site of the two was carried out. After interfering with circPUM1 expression in MIAPaCa-2 and PANC-1 cells, cell proliferation, viability, apoptosis rate, invasion ability, glucose consumption, and lactate production were measured by MTT, colony formation, flow cytometry, Transwell assays, and glucose and lactate assay kits. Additionally, western blot was utilized for assessing PI3K/AKT signaling pathway-related proteins. From the results, highly expressed circPUM1 and miR-200c-3p in PC tissues and cells were proved.

Results: Down-regulation of circPUM1 expression significantly inhibited cell proliferation, cell viability, invasion, and glycolysis, while increasing the apoptosis rate. Down-regulated circPUM1 led to the inhibition of the PI3K/AKT signaling pathway activity in PC cells, while up-regulated circPUM1 increased its activity. Further experiments revealed that down-regulation of miR-200c-3p expression reversed the inhibitory effect of lowly expressed circPUM1 on PC cells.

Conclusion: In summary, circPUM1 activates PI3K/AKT signaling pathway by sponging miR-200c-3p and promotes PC progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1389201022666210713152457DOI Listing
July 2021

Microneme Protein 6 Is Involved in Invasion and Egress by .

Pathogens 2021 Feb 13;10(2). Epub 2021 Feb 13.

National Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.

Background: , is the etiological agent of neosporosis, an infection that causes abortions in cattle and nervous system dysfunction in dogs. Invasion and egress are the key steps of the pathogenesis of infection. Microneme proteins (MICs) play important roles in the recognition, adhesion, and invasion of host cells in other apicomplexan parasites. However, some MICs and their functions in infection have rarely been reported.

Methods: The homologous recombination strategy was used to investigate the function of MIC6 in infection.

Results: ΔNcMIC6 showed a smaller plaque size and weakened capacities of invasion and egress than Nc1. Transcription levels of the egress-related genes CDPK1, PLP1, and AMA1 of ΔNcMIC6 were downregulated. Due to the lack of NcMIC6, virulence of the pathogen in the infected mouse was weakened. The subcellular localization of NcMIC1 and NcMIC4 in ΔNcMIC6, however, did not change. Nevertheless, the transcription levels of MIC1 and MIC4 in ΔNcMIC6 were downregulated, and the expression and secretion of MIC1 and MIC4 in ΔNcMIC6 were reduced compared with that in Nc1. Furthermore, the absence of NcMIC6 weakened the virulence in mice and lower parasite load detected in mice brains.

Conclusions: NcMIC6 is involved in host cell invasion and egress in and may work synergistically with other MICs to regulate the virulence of the pathogen. These data lay a foundation for further research into the function and application of NcMIC6.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/pathogens10020201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918358PMC
February 2021

Erratum to "miR-876 Inhibits EMT and Liver Fibrosis via POSTN to Suppress Metastasis in Hepatocellular Carcinoma".

Biomed Res Int 2020 12;2020:7043985. Epub 2020 Dec 12.

Hepatobiliary Surgery Institute, Southwest Hospital, Army Medical University, China.

[This corrects the article DOI: 10.1155/2020/1964219.].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/7043985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787729PMC
December 2020

Tumor-Linked Macrophages Promote HCC Development by Mediating the CCAT1/Let-7b/HMGA2 Signaling Pathway.

Onco Targets Ther 2020 14;13:12829-12843. Epub 2020 Dec 14.

Department of General Surgery, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong 518107, People's Republic of China.

Background: The role of high mobility group A2 (HMGA2) in the progression of hepatocellular carcinoma (HCC) is yet to be investigated, though tumor-associated macrophages (TAMs) are known to mediate the process.

Methods: Immunohistochemistry (IHC), Western blot, and real-time PCR assays were performed to identify HMGA2 and TAMs markers. The TAMs-like macrophages (TAMs-Mφs) were triggered with the help of 25 ng/mL hM-CSF and 50% NBCM. EdU assay wound healing assay, transwell assay, and TUNEL assay, as well as flow cytometry, were carried out to study the effect of HMGA2 or TAMs on the functioning of HCC cells.

Results: HCC tumor tissues were detected with upregulated HMGA2 and TAMs markers (CD68, CD163, and CD204); in addition, HMGA2 was positively correlated with TAMs markers. The proliferation, migration, and invasion of HepG2 cells were also observed to be stimulated by HMGA2. Remarkably, cell apoptosis was not affected by upregulated HMGA2, but HMAG2 inhibition was observed to intensify it. Also, the release of CSF1 was observed to be amplified by HMGA2. HMGA2-overexpressed-HepG2 cells promoted the migrating abilities of both M0-Mφs and TAMs-Mφs but were suppressed by HMGA2 down-regulated HepG2 cells. In addition, TAMs-Mφs supernatant regulated the CCAT1/let-7b/HMGA2 signaling pathway by intensifying the malignant biological behaviors.

Conclusion: HMGA2 stimulated TAMs-induced HCC progression, mediated by the CCAT1/let-7b/HMGA2 signaling pathway, TAMs aggravated HCC development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/OTT.S283786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751845PMC
December 2020

Prognostic Impact of Tumor-Infiltrating Lymphocytes in Laryngeal Squamous Cell Carcinoma Patients.

Laryngoscope 2021 04 27;131(4):E1249-E1255. Epub 2020 Oct 27.

Shanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.

Objectives/hypothesis: Tumor-infiltrating lymphocytes (TILs) has been shown to be associated with the prognosis of many tumors, yet few studies have investigated their roles in laryngeal squamous cell carcinoma (LSCC). We aim to investigate the prognostic values of tumor-infiltrating CD3 /CD4 /CD8 /Foxp3 T-cells and neutrophils in LSCC patients that received total or partial laryngectomy.

Study Design: Retrospective case series of LSCC patients who underwent total or partial laryngectomy from 2013 to 2014 at Eye, Ear, Nose, and Throat Hospital of Fudan University.

Methods: In our study, 41 tumor tissues from patients with LSCC were retrospectively assessed using immunohistochemistry for CD3 /CD4 /CD8 /Foxp3 T-cells and CD66b neutrophils. Overall survival (OS) and disease-free survival (DFS) were recorded using Kaplan-Meier methods.

Results: Generally, patients with high density of TILs (CD3, CD4, CD8) showed improved OS or DFS. Specifically, high density of CD3 TILs were associated with better OS, yet poorer OS and DFS for CD66b neutrophils. Patients with an Immunoscore of 0-1 experienced the worst OS and DFS, compared with Immunoscore 2-4 (P = .0111 for OS, P = .0391 for DFS). In Cox proportional hazards analysis adjusted for N stage and T stage, only stroma CD66b neutrophils densities were able to predict OS, with odds ratios of 4.819 (95% confidence interval [CI] 1.149-20.206; P = .032*), and DFS 2.888 (95% CI 1.043-7.997; P = .041*).

Conclusions: The density of TILs and CD66b neutrophils may help predict the prognosis of patients with LSCC after surgery.

Level Of Evidence: 3 Laryngoscope, 131:E1249-E1255, 2021.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lary.29196DOI Listing
April 2021

miR-876 Inhibits EMT and Liver Fibrosis via POSTN to Suppress Metastasis in Hepatocellular Carcinoma.

Biomed Res Int 2020 5;2020:1964219. Epub 2020 Oct 5.

Hepatobiliary Surgery Institute, Southwest Hospital, Army Medical University, China.

Background: The asymptomatic onset, frequent recurrence, and poor prognosis of hepatocellular carcinoma (HCC) prompted us to identify new therapeutic targets or predictive markers of HCC diagnosis or prognosis.

Methods: In this study, bioinformatics analysis was used to screen for target miRNAs from the open-access TCGA database. Transwell assays, Western blotting, and qRT-PCR analyses were used to detect cellular functions and gene expression in HCC cells and samples. A nude mouse tumorigenesis model was established to facilitate the observation of HCC progression. Other assays included luciferase reporter assays, IHC, and survival analysis.

Results: We found that the identified miR-876 from TCGA was expressed at low levels in HCC cell lines and that low miR-876 expression was corrected with liver cirrhosis, tumor thrombus, and TNM stage. Further research revealed that miR-876 regulated cell invasion, EMT, and collagen expression by targeting POSTN expression. miR-876 and POSTN were inversely correlated in HCC samples and associated with EMT status and liver fibrosis in clinical HCC tissues. miR-876 inhibited the liver cancer progression in animal assays. Finally, both miR-876 and POSTN were risk factors for HCC survival, and HCC patients with combined low miR-876 and high POSTN expression had worse prognosis.

Conclusions: miR-876 inhibited HCC EMT and fibrosis by targeting POSTN, thus affecting HCC progression and prognosis. miR-876 and POSTN may be useful therapeutic targets or prognostic markers of HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/1964219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559219PMC
May 2021

The Pathogenic Effects of on the Proliferation, Osteogenic Differentiation, and Transcriptome of Osteoblasts.

Front Cell Dev Biol 2020 11;8:807. Epub 2020 Sep 11.

Department of Human Microbiome, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University and Shandong Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, China.

As one of the most common oral diseases, periodontitis is closely correlated with tooth loss in middle-aged and elderly people. () contributes to periodontitis, but the evidence in alveolar bone loss is still unclear. In this study, cytological experiments and transcriptome analyses were performed to characterize the biological process abnormalities and the molecular changes of -stimulated osteoblasts. could inhibit cell proliferation, promote cell apoptosis, and elevate pro-inflammatory cytokine production of osteoblasts, and it also inhibited osteoblast differentiation and mineralized nodule formation and decreased the expression of osteogenetic genes and proteins. Whole-transcriptome analyses identified a total of 235 transcripts that were differentially expressed in all six time points, most of which were inflammation-related genes. The genes, , , , , , , , , , , , , and , played core roles in a PPI network, and interacted closely with other ones in the infection. In addition, 133 osteogenesis-related differential expression genes (DEGs) were time-serially dynamically changed in a short time-series expression miner (STEM) analysis, which were enriched in multiple cancer-related pathways. The core dynamic DEGs (, , , , , , , and ) had been reported to be closely related to the development and metastasis in tumor and cancer progress. This study is the first to evaluate the long-term interaction of on osteoblasts, which might increase the risk of cell carcinogenesis of normal osteoblasts, and provides new insight into the pathogenesis of bacterial-induced bone destruction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2020.00807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517582PMC
September 2020

Anti-PD-1 Immunotherapy and Radiotherapy for Stage IV Intrahepatic Cholangiocarcinoma: A Case Report.

Front Med (Lausanne) 2020 28;7:368. Epub 2020 Aug 28.

Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Due to the unsatisfactory robustness of current predictive biomarkers in many cases, application of immunotherapy in advanced cancers with limited treatment options, such as stage IV intrahepatic cholangiocarcinoma (ICC), was quite common. Hence, strategies to enhance the therapeutic effect of immunotherapy or to extend the scope of potential beneficial patients were urgently needed. Combination of radiotherapy and anti-programmed death receptor-1 (PD-1) immunotherapy was a promising one, since they were found to have a synergistic anti-tumor effect in animal models and a couple of patients. We here present a 68-years-old male with chemotherapy-intolerable stage IV ICC, whose primary tumor had low PD-L1 expression level, scarce CD8+ cells in tumor microenvironment, high microsatellite instability (MSI), and high tumor mutation burden (TMB). These biomarkers showed a conflicting prediction of the treatment response and clinical benefit of anti-PD-1 immunotherapy. Combination therapy of anti-PD-1 immunotherapy and radiotherapy was adopted as first-line treatment for the patient. After six cycles of immunotherapy, shrinkage of the primary liver tumor and metastatic lymph nodes happened, alongside with new lung metastasis, which indicated a mixed response. Radiotherapy was then administered to both the liver and lung lesions, accompanied with continued immunotherapy. The combined therapy eventually led to a complete response for both the primary tumor and all metastases without treatment-related adverse effects. The patient has survived for 26 months after the combined therapy and remains tumor-free currently. This case demonstrates the high inconsistency between immunotherapy response biomarkers and the synergetic anti-tumor effect of immunotherapy and radiotherapy in ICC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmed.2020.00368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485089PMC
August 2020

The safety, feasibility, and cost-effectiveness of early laparoscopic cholecystectomy for patients with mild acute biliary pancreatitis: A meta-analysis.

Surgeon 2020 Jul 21. Epub 2020 Jul 21.

Department of General Surgery, The Seventh Hospital of Sun Yat-sen University, China.

Background: It remains controversial on the optimal timing of cholecystectomy for patients with mild acute biliary pancreatitis. This study aimed at comparing the safety, feasibility, and cost-effectiveness of early laparoscopic cholecystectomy (ELC, within 72 h after admission) versus delayed laparoscopic cholecystectomy (DLC, beyond 72 h after admission) for patients with mild acute biliary pancreatitis.

Methods: We performed a systematic search in the following databases: PubMed, Embase, Web of Science, and Cochrane library. We only included articles from RCTs which designed to evaluate the complications, conversion to open cholecystectomy, recurrence of acute pancreatitis, the length of hospital stay, and costs between patients undergoing ELC and those undergoing DLC. We schemed to analyze data using STATA 15.0 with both the random-effects and the fixed-effect models. We computed relative risk (RR) and weighted mean difference (WMD) with 95% confidence intervals (CI) based on the intention-to-treat (ITT) analysis.

Results: A total of 4 studies involving 439 (215 vs 224) patients were included. The difference of complication rate [3.3% vs 3.2%; RR 1.03 (0.35, 3.01), P = 0.961] and rate of conversion to open cholecystectomy [3.8% vs 3.3%; RR 1.13 (0.37, 3.43), P = 0.830] are insignificant between patients who underwent ELC and ones who underwent DLC. The difference of rate of recurrence of acute pancreatitis is significant between ELC and DLC (2.17% vs 8.99%; RR 0.24 (0.08-0.70), P = 0.009). ELC does not shorten the length of hospital stay (random-effects model analysis: WMD -1.09 days (-2.67, 0.48), P = 0.173; fixed-effect model analysis: WMD -0.62 days (-1.00, -0.24), P = 0.001).

Conclusion: Compared to DLC, ELC is equally safe and feasible both in complication rate and rate of conversion to open procedure, and significantly reduces the recurrence rate of acute pancreatitis.

Prospero Registration Number: CRD42018116239.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.surge.2020.06.014DOI Listing
July 2020

Impacts of Absolute and Relative Income on Self-Rated Health in Urban and Rural China.

Int J Health Serv 2020 May 3:20731420922689. Epub 2020 May 3.

Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada.

This study aims to assess the impacts of absolute and relative income on self-rated health (SRH) of residents in rural and urban China. Data were derived from the China Health and Nutrition Survey. Three distinct measures of relative income were considered (Gini coefficient, Yitzhaki index, and Deaton index) and computed for 3 geographic units (nation, province, and community). Nonlinear dynamic models for panel data were employed to test the absolute and relative income hypotheses. Absolute income was significantly associated with SRH among urban and rural populations. Relative income, as measured by the Gini coefficient, the Yitzhaki index, and the Deaton index, had statistically significant and negative impacts on SRH among the rural population, regardless of the reference group. For the urban population, the Gini coefficient was associated with SRH regardless of the reference group. In contrast, only the Yitzhaki index and the Deaton index at the provincial level were associated with SRH among the urban population. Our findings may provide a reference for policymakers to implement health policies designed to improve population health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0020731420922689DOI Listing
May 2020

Pathogenic and antimicrobial resistance genes in Streptococcus oralis strains revealed by comparative genome analysis.

Genomics 2020 09 22;112(5):3783-3793. Epub 2020 Apr 22.

Department of Human Microbiome, School and Hospital of Stomatology, Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, No. 44-1 Wenhua Road West, 250012 Jinan, Shandong, China; State Key Laboratory of Microbial Technology, Shandong University,266237 Qingdao, Shandong, China; NHC Key Laboratory of Otorhinolaryngology (Shandong University), Jinan, Shandong, China. Electronic address:

Streptococcus oralis is an early colonizer bacterium in dental plaques and is considered a potential pathogen of infective endocarditis (IE) disease. In this study, we built a complete genome map of Streptococcus oralis strain SOT, Streptococcus oralis strain SOD and Streptococcus infantis strain SO and performed comparative genomic analysis among these three strains. The results showed that there are five genomic islands (GIs) in strain SOT and one CRISPR in strain SOD. Each genome harbors various pathogenic genes related to diseases and drug resistance, while the antibiotic resistance genes in strains SOT and SOD were quite similar but different from those in strain SO. In addition, we identified 17 main virulence factors and capsule-related genes in three strains. These results suggest the pathogenic potential of Streptococcus strains, which lay a foundation for the prevention and treatment of a Streptococcus oralis infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygeno.2020.04.014DOI Listing
September 2020

TRPV1 activation mitigates hypoxic injury in mouse cardiomyocytes by inducing autophagy through the AMPK signaling pathway.

Am J Physiol Cell Physiol 2020 05 15;318(5):C1018-C1029. Epub 2020 Apr 15.

State Key Laboratory of Trauma, Burns, and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.

Autophagy is a highly conserved self-protection mechanism that plays a crucial role in cardiovascular diseases. Cardiomyocyte hypoxic injury promotes oxidative stress and pathological alterations in the heart, although the interplay between these effects remains elusive. The transient receptor potential vanilloid 1 (TRPV1) ion channel is a nonselective cation channel that is activated in response to a variety of exogenous and endogenous physical and chemical stimuli. Here, we investigated the effects and mechanisms of action of TRPV1 on autophagy in hypoxic cardiomyocytes. In this study, primary cardiomyocytes isolated from C57 mice were subjected to hypoxic stress, and their expression of TRPV1 and adenosine 5'-monophosphate-activated protein kinase (AMPK) was regulated. The autophagy flux was assessed by Western blotting and immunofluorescence staining, and the cell viability was determined through Cell counting kit-8 assay and Lactate dehydrogenase assays. In addition, the calcium influx after the upregulation of TRPV1 expression in cardiomyocytes was examined. The results showed that the number of autophagosomes in cardiomyocytes was higher under hypoxic stress and that the blockade of autophagy flux aggravated hypoxic damage to cardiomyocytes. Moreover, the expression of TRPV1 was induced under hypoxic stress, and its upregulation by capsaicin improved the autophagy flux and protected cardiomyocytes from hypoxic damage, whereas the silencing of TRPV1 significantly attenuated autophagy. Our observations also revealed that AMPK signaling was activated and involved in TRPV1-induced autophagy in cardiomyocytes under hypoxic stress. Overall, this study demonstrates that TRPV1 activation mitigates hypoxic injury in cardiomyocytes by improving autophagy flux through the AMPK signaling pathway and highlights TRPV1 as a novel therapeutic target for the treatment of hypoxic cardiac disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/ajpcell.00161.2019DOI Listing
May 2020

BCL11A Promotes the Progression of Laryngeal Squamous Cell Carcinoma.

Front Oncol 2020 20;10:375. Epub 2020 Mar 20.

Shanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, Shanghai, China.

We report functional and clinical data uncovering the significance of B-cell lymphoma/leukemia 11A (BCL11A) in laryngeal squamous cell carcinoma (LSCC). We examined BCL11A expression in a cohort of LSCC patients and evaluated the association between BCL11A expression and clinicopathological features. We investigated the consequences of overexpressing BCL11A in the LSCC cell line on proliferation, migration, invasion, cell cycle, chemosensitivity, and growth . We explored the relationship between BCL11A and MDM2 in LSCC and tumorigenesis pathways by using the Human Cancer PathwayFinder Array. High levels of BCL11A were found in LSCC tissues and were more frequently associated with advanced lymphatic metastasis stages with poor prognoses. BCL11A overexpression enhanced LSCC proliferation and . A positive correlation between MDM2 and BCL11A expression was identified. These data uncover important functions of BCL11A in LSCC and identify BCL11A as a prognostic biomarker and potential therapeutic target in LSCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.00375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098986PMC
March 2020

Time-Course Transcriptome Analysis of Gingiva-Derived Mesenchymal Stem Cells Reveals That Triggers Oncogene Expression in the Process of Cell Differentiation.

Front Cell Dev Biol 2019 14;7:359. Epub 2020 Jan 14.

Department of Human Microbiome, School and Hospital of Stomatology, Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, China.

has pathogenic effects on oral squamous cell carcinoma and colon cancer, while the effects of continuously altered gene expression in normal human cells, as induced by persistent exposure to , remain unclear. In this study, a microarray Significant Profiles (maSigPro) analysis was used to obtain the transcriptome profile of gingiva-derived mesenchymal stem cells (GMSCs) stimulated by for 3, 7, 14, and 21 day, and the results revealed 790 (nine clusters) differentially expressed genes (DEGs), which were significantly enriched in cell adherens junctions and cancer-related pathways. On the basis of a short time-series expression miner (STEM) analysis, all the expressed genes in the GMSCs were grouped into 50 clusters according to dynamic gene expression patterns, and the expression levels of three gene clusters in the -treated GMSCs were significantly different than the predicted values. Among the 790 DEGs, 50 tumor-associated genes (TAGs; such as L3MBTL4, CD163, CCCND2, CADM1, BCL7A, and IGF1) and five core dynamic DEGs (PLCG2, CHI3L2, L3MBTL4, SH2D2A, and NLRP3) were identified during stimulation. Results from a GeneMANIA database analysis showed that PLCG2, CHI3L2, SH2D2A, and NLRP3 and 20 other proteins formed a complex network of which 12 genes were enriched in cancer-related pathways. Based on the five core dynamic DEGs, the related microRNAs (miRNAs) and transcription factors (TFs) were obtained from public resources, and an integrated network composed of the related TFs, miRNAs, and mRNAs was constructed. The results indicated that these genes were regulated by several miRNAs, such as miR-372-3p, miR-603, and miR-495-3p, and several TFs, including CREB3, GATA2, and SOX4. Our study suggests that long-term stimulation by may trigger the expression of cancer-related genes in normal gingiva-derived stem cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2019.00359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970952PMC
January 2020

Moderate-to-severe ovarian hyperstimulation syndrome: A retrospective multivariate logistic regression analysis in Chinese patients.

Adv Clin Exp Med 2020 Jan;29(1):85-90

Reproductive Medicine Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.

Background: Ovarian hyperstimulation syndrome (OHSS), a life-threatening complication occurring in stimulated ovarian cycles, arises from treatment with gonadotropin for inducing follicular maturation.

Objectives: The aim of this study was to compare the risk factors between patients with severe OHSS and those without OHSS after in vitro fertilization by intracytoplasmatic sperm injection/embryo transfer (IVF-ICSI/ET). Identifying the associated risk factors may provide guidance for clinicians on how to prevent OHSS.

Material And Methods: The retrospective study involved patients who had completed IVF-ICSI/ET cycles. The difference in markers for predicting the occurrence of OHSS between groups was compared. The potential protective and risk factors, as well as the predictive markers, were identified.

Results: Patients with OHSS were younger (p = 0.015), had higher basal antral follicle counts (AFC) (p < 0.001) and lower total dosages of gonadotropin (Gn) (p = 0.011). On the day of human chorionic gonadotropin (hCG) administration, significantly higher total numbers of follicles (p < 0.001), serum estradiol (E2) (p < 0.001) and progestrone (Pg) (p = 0.001) levels, numbers of oocytes (p < 0.001) and metaphase II (MII) oocytes (p < 0.001) were also observed in the OHSS group when compared to the non-OHSS group. A univariate regression analysis revealed that age (OR = 0.898, 95% CI = 0.822-0.981) and total dosage of Gn (OR = 0.999, 95% CI = 0.999-1.000) were protective factors, whereas AFC (OR = 1.090, 95% CI = 1.051-1.131) and, on the day of hCG injection, the number of follicles (OR = 1.185, 95% CI = 1.027-1.230), serum E2 (OR = 1.000, 95% CI = 1.000-1.000) and Pg (OR = 2.773, 95% CI = 0.510-3.370) levels, the number of oocytes (OR = 1.254, 95% CI = 0.894-1.472) and MII oocytes (OR = 1.238, 95% CI = 0.747-1.217) were risk factors for OHSS. However, a multivariate regression analysis showed that the total number of follicles (OR = 1.124, 95% CI = 1.027-1.230) was the only predictive factor for the occurrence of OHSS.

Conclusions: The study demonstrated that the follicle count measured on the day of hCG administration was the only predictive factor for the occurrence of OHSS. This provides basic guidance to clinicians on the prevention of the complication when using assisted reproductive technologies (ART).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.17219/acem/92916DOI Listing
January 2020

Persistent Exposure to Triggers Chemokine/Cytokine Release and Inhibits the Proliferation and Osteogenic Differentiation Capabilities of Human Gingiva-Derived Mesenchymal Stem Cells.

Front Cell Infect Microbiol 2019 17;9:429. Epub 2019 Dec 17.

Department of Human Microbiome, School and Hospital of Stomatology, Shandong University and Shandong Provincial Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, China.

is one of the most frequent pathogenic bacteria causing periodontitis. The direct effect of () on oral stem cells has rarely been reported. In this study, we aimed to evaluate how gingiva-derived mesenchymal stem cells (GMSCs) respond to a direct challenge with . GMSCs were isolated by the limiting dilution method and exposed to at various multiplicities of infection (MOIs; :cell ratios of 10:1, 50:1, and 100:1) for 24 h to 4 weeks. Our results indicated that significantly inhibited cell proliferation in a dose-dependent manner and promoted cell migration and the release of chemokines/cytokines, such as CCL2, CXCL1, and IL-6. Additionally, inhibited GMSC osteogenic differentiation partly by decreasing alkaline phosphatase (ALP) activity, mineralized nodule formation, and osteogenesis-related gene and protein expression. RNA-sequencing analyses indicated that time-dependently activated cellular signaling pathways during the process of osteogenic differentiation. A total of 64 cell differentiation-related genes were found to be differentially expressed between non-infected and -infected GMSCs at 3, 7, 14, and 21 d. Intriguingly, we discovered that the 64 cell differentiation-related differentially expressed genes (DEGs) were significantly enriched in cancer-related pathways, such as bone cancer, osteosarcoma and bone marrow cancer, which provides new insight into tumorigenesis during the process of GMSC osteogenic differentiation. In conclusion, this study demonstrates that persistent exposure to promotes cell migration and chemokine/cytokine release and inhibits the proliferation and osteogenic differentiation of GMSCs. Our study provides a novel and long-time bacteria-cell co-culture model and makes a foundation for the future mechanistic studies of GMSCs under infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcimb.2019.00429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927917PMC
July 2020

The role of in colorectal cancer: from carcinogenesis to clinical management.

Chronic Dis Transl Med 2019 Sep 1;5(3):178-187. Epub 2019 Oct 1.

Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong 518107, China.

Colorectal cancer (CRC) is a common malignant tumor that affects people worldwide. Metagenomic analyses have shown an enrichment of () in colorectal carcinoma tissue; many studies have indicated that is closely related to the colorectal carcinogenesis. In this review, we provide the latest information to reveal the related molecular mechanisms. The known virulence factors of promote adhesion to intestinal epithelial cells via FadA and Fap2. Besides, Fap2 also binds to immune cells causing immunosuppression. Furthermore, recruits tumor-infiltrating immune cells, thus yielding a pro-inflammatory microenvironment, which promotes colorectal neoplasia progression. was also found to potentiate CRC development through toll-like receptor 2 (TLR2)/toll-like receptor 4 (TLR4) signaling and microRNA (miRNA)-21 expression. In addition, increases CRC recurrence along with chemoresistance by mediating a molecular network of miRNA-18a*, miRNA-4802, and autophagy components. Moreover, viable was detected in mouse xenografts of human primary colorectal adenocarcinomas through successive passages. These findings indicated that an increased number of in the tissues is a biomarker for the diagnosis and prognosis of CRC, and the underlying molecular mechanism can probably provide a potential intervention treatment strategy for patients with -associated CRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cdtm.2019.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6926109PMC
September 2019

Cyclin-dependent kinase 7 inhibitor THZ1 in cancer therapy.

Chronic Dis Transl Med 2019 Sep 18;5(3):155-169. Epub 2019 Oct 18.

Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong 518107, China.

Current cancer therapies have encountered adverse response due to poor therapeutic efficiency, severe side effects and acquired resistance to multiple drugs. Thus, there are urgent needs for finding new cancer-targeted pharmacological strategies. In this review, we summarized the current understanding with THZ1, a covalent inhibitor of cyclin-dependent kinase 7 (CDK7), which demonstrated promising anti-tumor activity against different cancer types. By introducing the anti-tumor behaviors and the potential targets for different cancers, this review aims to provide more effective approaches to CDK7 inhibitor-based therapeutic agents and deeper insight into the diverse tumor proliferation mechanisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cdtm.2019.08.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6926117PMC
September 2019

Link between CIITA rs3087456 polymorphism and the risk of laryngeal squamous cell carcinoma in a Chinese population.

Pathol Res Pract 2020 Jan 18;216(1):152793. Epub 2019 Dec 18.

Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China. Electronic address:

The class II trans-activator (CIITA) is the master regulator of the major histocompatibility complex (MHC) gene expression. CIITA mutations have been previously associated with several kinds of tumors, while the role of CIITA polymorphisms (rs3087456) in laryngeal squamous cell carcinoma (LSCC) is little known. We evaluate the link between CIITA polymorphisms and the existence of LSCC in patients. This study was conducted with 200 Chinese Han patients (LSCC) and 200 healthy control subjects. The association of CIITA genetic polymorphism rs3087456 with the risk of LSCC was assessed through pyrosequencing. The CIITA expression in LSCC tumor tissue and adjacent normal tissue was detected by immunohistochemistry (IHC) staining. The relationship between the genotype of rs3087456 in controls and in clinical pathology features in LSCC were analyzed, and in-silico analysis was also used for the CIITA gene. The in-silico analysis results showed that the CIITA gene is closely related to genes such as RFX5 and RFXAP. The IHC results showed that CIITA was highly expressed in LSCC tumor tissues, compared with the corresponding adjacent normal tissues. The AG, AG + AA, and A genotypes of rs3087456 of CIITA gene notably increased the risk of LSCC compared to the controls. Our study suggests that CIITA polymorphism (rs3087456) is associated with a higher risk of developing LSCC in a Chinese cohort.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prp.2019.152793DOI Listing
January 2020

HIF-1-miR-219-SMC4 Regulatory Pathway Promoting Proliferation and Migration of HCC under Hypoxic Condition.

Biomed Res Int 2019 7;2019:8983704. Epub 2019 Nov 7.

Department of General Surgery, The Seventh Hospital of Sun Yat-sen University, Shenzhen, Guangdong Province 518107, China.

This paper aims to investigate the function of structural maintenance of chromosome 4 (SMC4) in the progression of hepatocellular carcinoma (HCC) under hypoxic condition. In this study, we found that suppression of SMC4 could inhibit proliferation and migration of HCC cells through inducing G1 phase arrest and affecting process of epithelial-mesenchymal transition (EMT) under hypoxic condition. Moreover, we demonstrated that SMC4 was transcriptionally regulated by hypoxia-inducible factor-1 (HIF-1) under hypoxic condition. As SMC has been shown to be a target gene of miR-219, we observed that miR-219 was downregulated under hypoxic condition and suppression of HIF-1a could lead to the upregulation of miR-219. We also proved that miR-219 could affect the proliferation and migration of HCC cells under hypoxic condition. In conclusion, our study demonstrated a novel HIF-1-miR-219-SMC4 regulatory pathway under hypoxic condition in HCC cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2019/8983704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885181PMC
April 2020

Facilitates Apoptosis, ROS Generation, and Inflammatory Cytokine Production by Activating AKT/MAPK and NF-B Signaling Pathways in Human Gingival Fibroblasts.

Oxid Med Cell Longev 2019 13;2019:1681972. Epub 2019 Oct 13.

Shandong Provincial Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, Shandong 250012, China.

() plays key roles in the initiation and progression of periodontitis. However, the pathogenic effect of on human oral tissues and cells has not been fully evaluated. In this study, we aimed to analyze the pathogenic effects of on human gingival fibroblasts (GFs) and clarify the potential mechanisms. RNA-sequencing analysis confirmed that significantly altered the gene expression of GF as the stimulation time increased. Cell counting and EdU-labeling assays indicated that inhibited GF proliferation and promoted cell apoptosis in a time- and dose-dependent manner. In addition, cell apoptosis, intracellular reactive oxygen species (ROS) generation, and proinflammatory cytokine production were dramatically elevated after stimulation. Furthermore, we found that the AKT/MAPK and NF-B signaling pathways were significantly activated by infection and that a large number of genes related to cellular proliferation, apoptosis, ROS, and inflammatory cytokine production downstream of AKT/MAPK and NF-B signaling pathways were significantly altered in -stimulated GFs. These findings suggest that inhibits GF proliferation and promotes cell apoptosis, ROS generation, and inflammatory cytokine production partly by activating the AKT/MAPK and NF-B signaling pathways. Our study opens a new window for understanding the pathogenic effects of periodontal pathogens on the host oral system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2019/1681972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6815639PMC
May 2020

Circ-ASH2L promotes tumor progression by sponging miR-34a to regulate Notch1 in pancreatic ductal adenocarcinoma.

J Exp Clin Cancer Res 2019 Nov 12;38(1):466. Epub 2019 Nov 12.

Hepatobiliary Surgery Institute, Southwest Hospital, Army Medical University, Chongqing, China.

Background: Circular RNAs (circRNAs) have recently been shown to play important roles in different tumors. However, their detailed roles and regulatory mechanisms in pancreatic ductal adenocarcinoma (PDAC) are not well understood. This study aimed to identify enriched circRNAs and detect their functions and mechanisms in PDAC cells and tissues.

Methods: circRNA-ASH2L (circ-ASH2L) was identified by circRNA microarray studies based on previous studies, and further detected in PDAC cells and samples by qRT-PCR. The functions of circ-ASH2L were identified by transwell, EdU, cell cycle or Tube formation assays. The regulatory mechanisms of circ-ASH2L were explored by WB, RIP, FISH, dual-luciferase assays, RNA pulldown or other assays.

Results: We identified a circRNA (circ-ASH2L) based on our previous studies, detected its expression in different malignant cells and found that circ-ASH2L was highly expressed in pancreatic cells or tumor tissues and correlated with tumor malignancy. Further studies revealed that circ-ASH2L promoted tumor invasion, proliferation and angiogenesis by regulating miR-34a, thus regulate Notch 1 expression. Circ-ASH2L served as a miRNA sponge for miR-34a and promoted tumor progression in vivo. Finally, we analyzed circ-ASH2L expression in clinical tissues and found that high circ-ASH2L expression was correlated with lymphatic invasion and TNM stage and was an independent risk factor for pancreatic patient survival.

Conclusions: circ-ASH2L play an important role in tumor invasion, and high circ-ASH2L may be a useful marker of PDAC diagnosis or progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13046-019-1436-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852927PMC
November 2019

The effects of compulsory health insurance on birth outcomes: evidence from China's UEBMI scheme.

BMC Health Serv Res 2019 Nov 1;19(1):779. Epub 2019 Nov 1.

Institute of Health Policy, Management, and Evaluation, University of Toronto, 155 College Street, Suite 425, Toronto, ON, M5T 3M6, Canada.

Background: Despite extensive research concerning the impact of health insurance on the advancement of infant health in developed countries, few studies have adjusted their results for potential confounding due to adverse selection in insurance coverage, wherein those who anticipate a need for health services tend to be the ones that acquire insurance. The presence of compulsory health insurance in China, such as the Urban Employee Basic Medical Insurance (UEBMI) scheme may provide an opportunity to estimate the effect of health insurance on infant health, by reducing the endogeneity problem into insurance due to the adverse selection. The objective is to assess the relationship between UEBMI and infant health outcomes in one sizeable municipal-level obstetrics hospital in Shanghai, East China.

Methods: Medical records data from the Shanghai First Maternity and Infant Hospital from January 1, 2013 to April 30, 2019 were used to form an analysis dataset of 160,429 live births which was comprised of Shanghai residents with UEBMI coverage (n = 101,153) and women without any insurance coverage (n = 59,276). A propensity score matching approach using conjoint quantile regression and probit regression models was used to eliminate latent endogeneity of UEBMI coverage in order to garner robust results. Further analysis stratified by maternal migrant status was conducted to further assess the sensitivity of the findings to distinct patient subgroups.

Results: The UEBMI scheme was shown to be associated with improvements in infant birth outcomes. The scheme was associated with: an increase in birth weight of about 30 g (p <  0.001, 95% CI 23.908-35.295). This finding was evident in other five different birth outcomes (premature birth, low birth weight, very low birth weight, low Apgar score, and an abnormal health condition at birth). After stratifying by migrant status, the UEBMI was shown to have a greater effect on migrants compared to local residents of Shanghai.

Conclusions: Our findings suggest that health insurance coverage for pregnant women, especially for migrants, has the potential to significantly and directly improve infant health outcomes. Further research is required to determine whether these findings can be replicated for other Chinese jurisdictions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12913-019-4657-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824087PMC
November 2019

Effects of Migration on Infant and Maternal Health in China.

Inquiry 2019 Jan-Dec;56:46958019884189

Institute of Health Policy, Management and Evaluation, University of Toronto, ON, Canada.

We assess the association between maternal migrant status and health outcomes in China, which has one of the world's largest migrant populations. Health records from the Shanghai First Maternity and Infant Hospital from January 1, 2013, to June 30, 2017, were used to analyze 104 681 live births for Shanghai native-born and migrant women based on diagnosis codes and demographic data. Regression analysis including propensity score matching was conducted to investigate the association between maternal migrant status and adverse infant birth outcomes (fetal disease, congenital malformation, neonatal disease) and maternal health after controlling for pregnancy status and socioeconomic factors. The results demonstrate that migrant women had statistically significant increased odds (9.1%-10%, < .001) of having infants with adverse health outcomes compared with their urban counterparts and that migrant mothers have less likelihood of pregnancy complications and gestational diabetes mellitus. Our results show the mixed effects of migration on infant and maternal health may be a possible outcome of China's Hukou system that often represents an important barrier in accessing prenatal health care by migrant women. Current reforms that improve access to prenatal health care services for migrant women may enhance the health outcomes of their infants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0046958019884189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6820187PMC
February 2020

Time-Course Transcriptome Analysis for Drug Repositioning in -Infected Human Gingival Fibroblasts.

Front Cell Dev Biol 2019 20;7:204. Epub 2019 Sep 20.

Department of Human Microbiome, School and Hospital of Stomatology, Shandong University and Shandong Provincial Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, China.

() is a crucial periodontal pathogen and human gingival fibroblasts (GFs) are the first line of defense against oral pathogens. However, the research on potential molecular mechanisms of host defense and effective treatment of infection in GFs remains scarce. In this study, we undertook a time-series experiment and performed an RNA-seq analysis to explore gene expression profiles during the process of infection in GFs. Differentially expressed genes (DEGs) could be divided into three coexpression clusters. Functional analysis revealed that the immune-related signaling pathways were more overrepresented at the early stage, while metabolic pathways were mainly enriched at the late stage. We computationally identified several U.S. Food and Drug Administration (FDA)-approved drugs that could protect the infected GFs via a coexpression-based drug repositioning approach. Biologically, we confirmed that six drugs (etravirine, zalcitabine, wortmannin, calcium D-pantothenate, ellipticine, and tanespimycin) could significantly decrease -induced reactive oxygen species (ROS) generation and block the Protein Kinase B (PKB/AKT)/mitogen-activated protein kinase signaling pathways. Our study provides more detailed molecular mechanisms of the process by which infects GFs and illustrates the value of the cogena-based drug repositioning method and the potential therapeutic application of these tested drugs in the treatment of infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2019.00204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771468PMC
September 2019

Long non-coding RNA TGLC15 advances hepatocellular carcinoma by stabilizing Sox4.

J Clin Lab Anal 2020 Jan 8;34(1):e23009. Epub 2019 Sep 8.

Department of General Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.

Background: The hepatocellular carcinoma (HCC) belongs to a common malignancy especially in China. Recent data have clarified important roles of long non-coding RNAs (lncRNAs) in HCC. However, the role of a novel intergenic lncRNA termed TGLC15 is still elusive.

Methods: We screened for novel lncRNAs using lncRNA profiling. TGLC15 expression was quantified by qRT-PCR. In vitro experiments such as migration and viability assays were performed. In vivo implantation experiments were conducted to investigate tumorigenic functions of TGLC15. Combined RNA immunoprecipitation (RIP) and mass spectrometry (MS) were utilized to uncover Sox4 as TGLC15 binding protein.

Results: TGLC15 is significantly overexpressed in tumor tissues and HCC cell lines. Higher TGLC15 levels correlated with advanced malignant characteristics such as TNM stages, tumor size, and metastasis. TGLC15 advanced HCC migration and viability. The in vivo experiments supported that xenograft tumor growth and proliferation were facilitated by TGLC15 overexpression. Mechanistic studies showed that TGLC15 interacted with Sox4 and interaction between TGLC15 and Sox4 could stabilize Sox4 via reduction in proteasome-mediated degradation.

Conclusions: Collectively, our data have identified a novel lncRNA TGLC15 during HCC development. The TGLC15-Sox4 signaling might be a potential target for pharmaceutical intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcla.23009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6977111PMC
January 2020
-->