Publications by authors named "Dan Liao"

126 Publications

circRNA_0006470 promotes the proliferation and migration of gastric cancer cells by functioning as a sponge of miR-27b-3p.

Neoplasma 2021 Oct 11. Epub 2021 Oct 11.

Department of Clinical Laboratory, SSL Central Hospital of Dongguan City, Affiliated Dongguan Shilong People's Hospital of Southern Medical University, Dongguan, Guangdong, China.

Cancer pathogenesis is influenced by epigenetic alterations mediated by circular RNAs (circRNAs). In this study, we aimed to investigate the regulatory mechanisms and cytological function of hsa_circ_0006470/miR-27b-3p in gastric cancer (GC). CircRNA and microRNA expression in cancer cells were measured by the qRT-PCR method. A dual-luciferase reporter assay was performed to validate the binding of hsa_circ_0006470 with miR-27b-3p. hsa_circ_0006470 was silenced in AGS cells, and proliferation, migration, and invasion were tested via the CCK-8 assay and Transwell system, respectively. The autophagy in GC cells was assessed by marker protein detection and transmission electron microscope. The results showed that hsa_circ_0006470 expression was significantly elevated in GC cells, which was mainly distributed in cytoplasmic components and could directly bind with miR-27b-3p in GC cells. Silencing of hsa_circ_0006470 repressed cell proliferation, migration, and invasion, which may be through regulating miR-27b-3p/Receptor tyrosine kinase-like orphan receptor 1 (ROR1). Silencing of hsa_circ_0006470 also elevated LC3II and Beclin-1 and suppressed p62 protein abundances, which subsequently induced autophagy in AGS cells. Furthermore, we found that hsa_circ_0006470 promotes phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PI3KCA) expressing by sponging miR-27b-3p. In conclusion, hsa_circ_0006470 promoted GC cell proliferation and migration through targeting miR-27b-3p and suppressing autophagy machinery.
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http://dx.doi.org/10.4149/neo_2021_210222N235DOI Listing
October 2021

Clinical evidence of the effects of carnitine supplementation on body weight, glycemic control and serum lipids in women with polycystic ovary syndrome: a systematic review and meta-analysis.

Gynecol Endocrinol 2021 Oct 11:1-6. Epub 2021 Oct 11.

Department of Gynaecology, SSL Central Hospital of Dongguan, Dongguan Third People's Hospital, Affiliated Dongguan Shilong People's Hospital of Southern Medical University, Dongguan, Guangdong, China.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. Several clinical trials have investigated the influence of carnitine on metabolic variables in PCOS, but have yielded conflicting results. This study aimed to summarize the clinical evidence of the effects of carnitine on weight management, glycemic and serum lipids controls in women with PCOS by conducting a meta-analysis of randomized control trials (RCTs). PubMed, Embase, Web of Sciences, Scopus, and the CENTRAL database were searched from inception to March 2021 for eligible articles. Study selection and assessment of quality were conducted independently by two investigators. Effect sizes for each outcome were reported with the weighted mean differences (WMDs) and 95% confidence intervals (CIs). The statistical heterogeneity of the included clinical trials was tested using the statistic. Six studies with 672 PCOS participants were included for meta-analysis. Our results revealed that carnitine supplements significantly decreased total cholesterol, low-density lipoprotein-cholesterol, triglycerides, body weight, body mass index, hip circumference, and waist circumference (All < .05). In addition, carnitine intervention also improved the levels of high-density lipoprotein cholesterol. However, no significant changes were seen in glucose homeostasis parameters. These results were stable after sensitivity analysis, and no significant publication biases were detected. Based on current evidence, carnitine supplementation in women with PCOS had beneficial effects on weight loss and lipid profiles. Further large-scale, well-designed RCTs are required to confirm these results.
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http://dx.doi.org/10.1080/09513590.2021.1988559DOI Listing
October 2021

Enhanced Conductivity and Antibacterial Behavior of Cotton via the Electroless Deposition of Silver.

Molecules 2021 Aug 5;26(16). Epub 2021 Aug 5.

Department of Chemistry, Faculty of Science, Sohag University, Sohag 82524, Egypt.

In this study, the surface-initiated atom transfer radical polymerization (SI-ATRP) technique and electroless deposition of silver (Ag) were used to prepare a novel multi-functional cotton (Cotton-Ag), possessing both conductive and antibacterial behaviors. It was found that the optimal electroless deposition time was 20 min for a weight gain of 40.4%. The physical and chemical properties of Cotton-Ag were investigated. It was found that Cotton-Ag was conductive and showed much lower electrical resistance, compared to the pristine cotton. The antibacterial properties of Cotton-Ag were also explored, and high antibacterial activity against both and was observed.
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http://dx.doi.org/10.3390/molecules26164731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401601PMC
August 2021

Source apportionment of PM and sulfate formation during the COVID-19 lockdown in a coastal city of southeast China.

Environ Pollut 2021 Oct 11;286:117577. Epub 2021 Jun 11.

Center for Excellence in Regional Atmospheric Environment, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021, China; Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021, China. Electronic address:

Revealing the changes in chemical compositions and sources of PM is important for understanding aerosol chemistry and emission control strategies. High time-resolved characterization of water-soluble inorganic ions, elements, organic carbon (OC), and elemental carbon (EC) in PM was conducted in a coastal city of southeast China during the COVID-19 pandemic. The results showed that the average concentration of PM during the city lockdown (CLD) decreased from 46.2 μg m to 24.4 μg m, lower than the same period in 2019 (PM: 37.1 μg m). Concentrations of other air pollutants, such as SO, NO, PM, OC, EC, and BC, were also decreased by 27.3%-67.8% during the CLD, whereas O increased by 28.1%. Although SO decreased from 4.94 μg mto 1.59 μg m during the CLD, the concentration of SO (6.63 μg m) was comparable to that (5.47 μg m) during the non-lockdown period, which were attributed to the increase (16.0%) of sulfate oxidation rate (SOR). O (O+NO) was positively correlated with SO, suggesting the impacts of photochemical oxidation. A good correlation (R = 0.557) of SO and Fe and Mn was found, indicating the transition-metal ion catalyzed oxidation. Based on positive matrix factorization (PMF) analysis, the contribution of secondary formation to PM increased during the epidemic period, consisting with the increase of secondary organic carbon (SOC), while other primary sources including traffic, dust, and industry significantly decreased by 9%, 8.5%, and 8%, respectively. This study highlighted the comprehensive and nonlinear response of chemical compositions and formation mechanisms of PM to anthropogenic emissions control under relatively clean conditions.
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http://dx.doi.org/10.1016/j.envpol.2021.117577DOI Listing
October 2021

Clinical Study of Paliperidone Palmitate Long-Acting Injection Combined With Electroacupuncture in the Treatment of Methamphetamine Addicts.

Front Pharmacol 2021 17;12:698740. Epub 2021 Jun 17.

Department of Psychiatry, Wuhan Wudong Hospital, Wuhan, China.

To explore the clinical efficacy of paliperidone palmitate long-acting injection combined with electroacupuncture in the treatment of methamphetamine addicts. This study focused on methamphetamine addicts who were admitted to our hospital from January 2020 to December 2020 as the main research object, with a total of 89 cases. The patients were divided into a control group of 45 cases and a study group of 44 cases according to the treatment method. The control group was treated with electroacupuncture, and the study group was treated with paliperidone palmitate long-acting injection on the basis of electroacupuncture in the control group. After 6 months of continuous treatment, the treatment effect of methamphetamine withdrawal symptom score before and after treatment was used; Hamilton Anxiety Scale score and Hamilton Depression Scale were used to compare the anxiety and depression situation of the two groups; the brain wave α and θ wave situation of the two groups were compared. The results showed that there was no significant difference in the scores of Ma withdrawal symptoms, Hamilton Anxiety and Hamilton Depression between the two groups before treatment ( < 0.05); after 3 and 6 months of treatment, the scores of Ma withdrawal symptoms, Hamilton Anxiety and Hamilton Depression in the study group were significantly lower than those in the control group and the difference was statistically significant ( < 0.05); 6 months after the completion of the treatment, the α wave amplitude and Fourier transformed α brain wave (FFT) in the study group were significantly higher than those in the control group, and the difference was statistically significant ( < 0.05). Paliperidone palmitate long-acting injection combined with electroacupuncture is better than electroacupuncture alone in the treatment of methamphetamine addicts, and can significantly improve anxiety, depression and brain waves, thereby preventing addicts from relapse.
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http://dx.doi.org/10.3389/fphar.2021.698740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245672PMC
June 2021

Correction to: Chromobox Homolog 4 is Correlated with Prognosis and Tumor Cell Growth in Hepatocellular Carcinoma.

Ann Surg Oncol 2021 Jul 2. Epub 2021 Jul 2.

State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.

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http://dx.doi.org/10.1245/s10434-021-10400-8DOI Listing
July 2021

Air pollution increases human health risks of PM-bound PAHs and nitro-PAHs in the Yangtze River Delta, China.

Sci Total Environ 2021 May 27;770:145402. Epub 2021 Jan 27.

Center for Excellence in Regional Atmospheric Environment, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China; Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China. Electronic address:

Identifying the nature and extent of atmospheric PM-bound toxic organic pollutants is beneficial to evaluate human health risks of air pollution. Seasonal observations of PM-bound polycyclic aromatic hydrocarbons (PAHs) and nitro-PAHs (NPAHs) in the Yangtze River Delta (YRD) were investigated, along with criteria air pollutants and meteorological parameters. With the elevated PM level, the percentage of 4-ring PAHs and typical NPAH including 3-Nitrobiphenyl (3-NBP) and 2-Nitrofluoranthene (2-NFLT) increased by 19-40%. PM-bound 2-NFLT was positively correlated with O and NO, suggesting the contribution of atmospheric oxidation capacity to enhance the secondary formation of NPAHs in the atmosphere. Positive matrix factorization (PMF) analysis indicated that traffic emissions (44.9-48.7%), coal and biomass combustion (27.6-36.0%) and natural gas and volatilization (15.3-27.5%) were major sources of PAHs, and secondary formation (39.8-53.8%) was a predominant contributor to total NPAH concentrations. Backward trajectory analysis showed that air masses from North China transported to the YRD region increased PAH and NPAH concentrations. Compare to clean days, the BaP equivalent concentrations of total PAHs and NPAHs during haze pollution days were enhanced by 10-25 and 2-6 times, respectively. The Incremental Lifetime Cancer Risks (ILCRs) of PAHs by inhalation exposure also indicated high potential health risks in the YRD region. The results implied that the health risks of PM-bound PAHs and NPAHs could be sharply enhanced with the increase of PM concentrations.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145402DOI Listing
May 2021

Meta-analysis of procalcitonin as a predictor for acute kidney injury.

Medicine (Baltimore) 2021 Mar;100(10):e24999

Department of Nephrology.

Background: Procalcitonin (PCT) was used for predicting the development of acute kidney injury (AKI) in several studies recently. We aimed to investigate the accuracy of PCT for predicting AKI in this study.

Methods: Studies that assessed the predictive performance of PCT for the development of AKI in adult patients were searched from Medline, Embase, and the Cochrane Library from inception to June 2020. We calculated the pooled sensitivities and specificities and the area under the summary receiver-operating characteristic (SROC) curves. I2 was used to test the heterogeneity and the potential heterogeneity was investigated by meta-regression.

Results: In total, 9 of 119 studies with 4852 patients were included, 1272 were diagnosed with AKI. In the overall analysis, the area under the SROC curve was 0.82 (95% CI, 0.79-0.85) and the pooled sensitivity and specificity were 0.76 (95% confidence interval [CI], 0.64-0.85) and 0.75 (95% CI, 0.61-0.86), respectively. In the subgroup analysis among septic patients, the pooled sensitivity and specificity were 0.59 (95% CI, 0.29-0.84) and 0.53 (95% CI, 0.31-0.74), and the area under the SROC was 0.57 (95% CI, 0.53-0.62).

Conclusion: PCT may be a potential predictor for the development of AKI.
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http://dx.doi.org/10.1097/MD.0000000000024999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969283PMC
March 2021

Combined targeting of vascular endothelial growth factor C (VEGFC) and P65 using miR-27b-3p agomir and lipoteichoic acid in the treatment of gastric cancer.

J Gastrointest Oncol 2021 Feb;12(1):121-132

Department of Clinical Laboratory, SSL Central Hospital of Dongguan City, Dongguan Third Clinical Hospital of Guangdong Medical University, Dongguan, China.

Background: Gastric cancer is the second leading cancer-related mortality worldwide and more effective treatment strategies are urgently needed to combat the disease. Using lipoteichoic acid (LTA) and miR-27b-3p agomir, we aimed to assess the efficacy of this combination of therapies in treating gastric cancer.

Methods: The RNA levels of miR-27b-3p, FOXO3, MET, KRAS, vascular endothelial growth factor C (VEGFC), TSC1, and P65 were analyzed by quantified-PCR (Q-PCR) and the cell viability of AGS cells was analyzed by MTT. Confirm Luciferase reporter assays were used to explore the putative miR-27b-3p binding sites and Western blot analyzed the protein level of GAPDH, VEGFC, P65, AKT, and phosphorylated-AKT (p-AKT). The level of P65 in both the cytoplasm and nucleus of AGS cells was visualized by immunofluorescence assay. Subcutaneous xenograft models of gastric cancer were established, and mice were treated with miR-27b-3p agomir, LTA, or both. Hematoxylin-eosin staining and Ki-67 immunohistochemistry analysis of tumor tissues were then performed.

Results: The results showed that the decreased expression of miR-27b-3p in gastric cancer cell lines inhibited the viability of AGS cells, and VEGFC was confirmed as the target of miR-27b-3p. In addition, ectopic expression of miR-27b-3p significantly inhibited the AKT pathway in AGS and N87 cells, and LTA suppressed the proliferation of gastric cancer cells by inhibiting the NF-κB pathway. In an established xenograft model, both miR-27b-3p agomir alone and LTA treatment alone inhibited tumor growth and treatment which combined the two showed an even stronger inhibitory effect.

Conclusions: Taken together, the combined use of LTA and miR-27b-3p agomir exhibited a synergistic effect in the treatment of gastric cancer.
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http://dx.doi.org/10.21037/jgo-21-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944161PMC
February 2021

Toward human intervention-free clinical diagnosis of intracranial aneurysm via deep neural network.

Patterns (N Y) 2021 Feb 22;2(2):100197. Epub 2021 Jan 22.

BNRist and Department of Automation, Tsinghua University, Beijing, Beijing 100084, China.

Intracranial aneurysm (IA) is an enormous threat to human health, which often results in nontraumatic subarachnoid hemorrhage or dismal prognosis. Diagnosing IAs on commonly used computed tomographic angiography (CTA) examinations remains laborious and time consuming, leading to error-prone results in clinical practice, especially for small targets. In this study, we propose a fully automatic deep-learning model for IA segmentation that can be applied to CTA images. Our model, called Global Localization-based IA Network (GLIA-Net), can incorporate the global localization prior and generates the fine-grain three-dimensional segmentation. GLIA-Net is trained and evaluated on a big internal dataset (1,338 scans from six institutions) and two external datasets. Evaluations show that our model exhibits good tolerance to different settings and achieves superior performance to other models. A clinical experiment further demonstrates the clinical utility of our technique, which helps radiologists in the diagnosis of IAs.
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http://dx.doi.org/10.1016/j.patter.2020.100197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892358PMC
February 2021

Clinical evidence of dietary supplementation with sesame on cardiovascular risk factors: An updated meta-analysis of randomized controlled trials.

Crit Rev Food Sci Nutr 2021 Feb 22:1-11. Epub 2021 Feb 22.

Department of Gynaecology, SSL Central Hospital of Dongguan, Affiliated Dongguan Shilong People's Hospital of Southern Medical University, Dongguan, Guangdong, China.

The present analysis was to summarize the evidence of the effects of sesame and its derivatives supplementation on cardiovascular disease (CVD) risk factors by performing a meta-analysis of randomized controlled trials (RCTs). Electronic databases were searched from their inception to July 2020. Two investigators independently assessed articles for inclusion, extracted data, and statistical analysis. The quality of included articles was assessed according to the Cochrane risk of bias tool. Major outcomes were synthesized using a random effect model and presented as weighted mean difference and 95% confidence interval. Heterogeneity, subgroup analyses, sensitivity analysis, meta-regression, and publication bias were also conducted. The GRADE approach was used to evaluate the quality of evidence. Overall, 16 trials involving 908 participants were included for statistical pooling. Compared with the control group, sesame intake significantly decreased the levels of total cholesterol, triglycerides, systolic blood pressure, diastolic blood pressure, body weight, body mass index, hip circumference, and waist circumference ( < 0.05). These results were stable in sensitivity analysis, and no significant publication bias was detected. Our findings provided evidence that sesame consumption may reduce the risk of CVD by improving blood lipids, blood pressure, and body weight management. Further large-scale, well-designed RCTs are required to confirm these results.
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http://dx.doi.org/10.1080/10408398.2021.1888689DOI Listing
February 2021

Rab22a-NeoF1 fusion protein promotes osteosarcoma lung metastasis through its secretion into exosomes.

Signal Transduct Target Ther 2021 Feb 11;6(1):59. Epub 2021 Feb 11.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.

It remains unknown for decades how some of the therapeutic fusion proteins positive in a small percentage of cancer cells account for patient outcome. Here, we report that osteosarcoma Rab22a-NeoF1 fusion protein, together with its binding partner PYK2, is sorted into exosomes by HSP90 via its KFERQ-like motif (RVLFLN). The exosomal Rab22a-NeoF1 fusion protein facilitates the pulmonary pre-metastatic niche formation by recruiting bone marrow-derived macrophages. The exosomal PYK2 activates RhoA in its negative recipient osteosarcoma cells and induces signal transducer and activator of transcription 3 activation in its recipient macrophages to increase M2 phenotype. Consequently, lung metastases of its recipient osteosarcoma cells are promoted by this exosomal Rab22a-NeoF1 fusion protein, and this event can be targeted by disrupting its interaction with PYK2 using a designed internalizing RGD peptide.
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http://dx.doi.org/10.1038/s41392-020-00414-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876000PMC
February 2021

Novel IL36RN Mutation Identified in Pediatric-Onset Generalized Pustular Psoriasis Causes IL36 Antagonist Degradation.

J Clin Immunol 2021 04 7;41(3):701-704. Epub 2021 Jan 7.

Pediatric Research Institute; Ministry of Education Key Laboratory of Child Development and Disorders; Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders; National Clinical Research Center for Child Health and Disorders; China International Science and Technology Cooperation base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, People's Republic of China.

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http://dx.doi.org/10.1007/s10875-020-00944-xDOI Listing
April 2021

Evaluation of the Diagnostic Value of Peripheral Blood Parameters for Neonatal Pneumonia.

Clin Lab 2020 Nov;66(11)

Background: To evaluate the diagnostic value of peripheral blood parameters including white blood cell (WBC), neutrophil, lymphocyte, monocyte, platelet, mean platelet volume (MPV), platelet distribution width (PDW), mean corpuscular volume (MCV), red cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte (MLR), platelet-to-lymphocyte ratio (PLR) and platelet-to-neutrophil ratio (PNR) for neonatal pneumonia.

Methods: Two hundred and six full-term neonates in our hospital from January 2018 to December 2019 were enrolled, including 73 pneumonic neonates and 133 health controls. Peripheral blood parameters were measured by an automatic blood cell analyzer. While C-reactive protein (CRP) and PCT concentrations were detected by electrochemical luminescence assay. Clinical signs, characteristic population, temperature, and chest radiograph findings were recorded. The receiver operating characteristic (ROC) curve was used to determine the cutoff values and analyze the diagnosis significances for neonatal pneumonia.

Results: This study showed that WBC, neutrophil, RDW, NLR, and MLR levels in the pneumonic group were higher than that of the control group, whereas lymphocyte, monocyte, platelet, and PNR levels were lower (p < 0.05). The ROC curve result showed that NLR and PNR owned higher AUC values than the rest of peripheral blood variables. At a cutoff value 2.581, NLR exhibited 63.01% sensitivity, 90.98% specificity, and 0.847 area under ROC curve (AUC). In addition, at a cutoff value 52.77, PNR showed 84.93% sensitivity, 78.95% specificity, and 0.856 AUC.

Conclusions: This study clarifies that peripheral blood parameter of NLR and PNR have good applied value in diagnosis neonatal pneumonia with high sensitivity and specificity.
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http://dx.doi.org/10.7754/Clin.Lab.2020.200407DOI Listing
November 2020

Pharmacological inhibition of fatty acid-binding protein 4 alleviated kidney inflammation and fibrosis in hyperuricemic nephropathy.

Eur J Pharmacol 2020 Nov 17;887:173570. Epub 2020 Sep 17.

Division of Nephrology and National Clinical Research Center for Geriatrics, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu, 610041, China.

Hyperuricemia is an independent risk factor for chronic kidney disease (CKD). Excessive uric acid (UA) level in the blood leads to hyperuricemic nephropathy (HN), which is characterized by glomerular hypertension, arteriolosclerosis and tubulointerstitial fibrosis. Fatty acid binding protein 4 (FABP4) is a potential mediator of inflammatory responses which contributes to renal interstitial fibrosis. However, the roles of FABP4 in HN remains unknown. In the study, a mouse model of HN induced by feeding a mixture of adenine and potassium oxonate, severe kidney injury and interstitial fibrosis, as well as the increased kidney-expressed FABP4 protein level were evident, accompanied by the activation of inflammatory responses. Oral administration of BMS309403, a highly selective FABP4 inhibitor, improved renal dysfunction, inhibited the mRNA level of KIM-1 and NGAL, as well as reduced the expression of proinflammatory cytokines and fibrotic proteins in the injured kidneys. BMS309403 treatment also inhibited the FABP4 activity and further suppressed the activation of JAK2-STAT3 and NF-kB P65 signaling pathways in the hyperuricemia-injured kidneys and UA-stimulated human tubular epithelial (HK-2) cells, respectively. In summary, our study for the first time demonstrated that FABP4 played a crucial role in kidney inflammation and fibrosis via the regulation of JAK2-STAT3 and NF-kB P65 pathways in HN mice. The results suggested that FABP4 inhibition might be a promising therapeutic strategy for HN.
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http://dx.doi.org/10.1016/j.ejphar.2020.173570DOI Listing
November 2020

LncRNA FAM230B Promotes Gastric Cancer Growth and Metastasis by Regulating the miR-27a-5p/TOP2A Axis.

Dig Dis Sci 2021 08 10;66(8):2637-2650. Epub 2020 Sep 10.

Department of Clinical Laboratory, SSL Central Hospital of Dongguan City, Affiliated Dongguan Shilong People's Hospital of Southern Medical University, 1 Xianglong Road, Dongguan City, 510080, Guangdong Province, China.

Aim: Long non-coding RNAs serve as key components of competing endogenous RNA (ceRNA) networks that underlie tumorigenesis. We investigated the pathogenic roles of lncRNA FAM230B and its molecular mechanism in gastric cancer (GC).

Method: The levels of FAM230B expression in five gastric cancer cell lines and in human gastric mucosal cells were compared by quantitative RT-PCR. To analyze the function of FAM230B in GC, we overexpressed FAM230B in AGS cells, silenced FAM230B in MGC-803 cells, and tested the effect of FAM230B on tumor growth in nude mice. The interaction between miR-27a-5p and FAM230B was predicted by a bioinformatics analysis and then verified with a dual-luciferase reporter assay. We also further investigated the role and mechanism of FAM230B by forcing overexpression of miR-27a-5p in MGC-803 gastric cancer cells.

Results: We found that FAM230B was highly expressed in gastric cancer cell lines and mainly located in the cytoplasm. FAM230B overexpression promoted the proliferation, migration, and invasion of AGS cells and repressed their apoptosis; it also facilitated tumor growth in vivo. In contrast, FAM230B knockdown suppressed the proliferation, migration, and invasion of MGC0803 cells, but enhanced their apoptosis and inhibited tumor growth in vivo. MiR-27a-5p expression was suppressed by FAM230B overexpression in AGS cells. MiR-27a-5p inhibited the proliferation, migration, and invasion of gastric cancer cells, and promoted the apoptosis of gastric cancer cells by reducing TOP2A (topoisomerase 2 alpha) expression.

Conclusion: Our study showed that lncRNA FAM230B might function to promote GC. FAM230B functioned as a ceRNA by sponging miR-27a-5p and enhancing TOP2A expression.
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http://dx.doi.org/10.1007/s10620-020-06581-zDOI Listing
August 2021

Acetylation dependent functions of Rab22a-NeoF1 Fusion Protein in Osteosarcoma.

Theranostics 2020 19;10(17):7747-7757. Epub 2020 Jun 19.

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.

Rab22a-NeoF1 fusion gene containing the 1-38aa of Rab22a (Rab22a) plays a decisive role in driving tumor metastasis by activating RhoA via binding to SmgGDS607. However, its intercellular regulation remains unknown. The Lys7 (K7) acetylation of Rab22a-NeoF1 was initially identified by mass spectrum. Co-transfection, immunoprecipitation and Western blotting were used to characterize the acetyltransferases and deacetylases responsible for the K7 acetylation of Rab22a-NeoF1, and to define the interaction of proteins. The specificity of K7 acetylation of Rab22a-NeoF1 was determined by its specific anti-K7ac-Rab22a-NeoF1 antibody and its K7R mutant. RhoA-GTP was measured by RhoA activation assay. The migration and invasion were assessed by Transwell assay without and with Matrigel matrix, respectively. The orthotopic osteosarcoma metastasis model was used to monitor the lung metastases of U2OS/MTX300-Luc stably expressing Vector, Rab22a-NeoF1 or its K7R mutant with or without C646, a relatively specific inhibitor of p300/CBP. The unpaired Student test was used for the statistical significance. The K7 of Rab22a-NeoF1 is acetylated by p300/CBP while is de-acetylated by both HDAC6 and SIRT1. The K7R mutant of Rab22a-NeoF1 lacks its binding to SmgGDS607 and subsequently lost its promoting functions, such as activation of RhoA, cell migration, invasion and lung metastasis in osteosarcoma and o, which are also diminished by p300/CBP inhibitor C646. The promoting function of Rab22a-NeoF1 is dependent on its K7 acetylation in osteosarcoma, and targeting this acetylation (e.g., C646) may benefit cancer patients, in particular osteosarcoma patients, who are positive for the Rab22a.
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http://dx.doi.org/10.7150/thno.46082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359080PMC
May 2021

Antiviral activities of resveratrol against rotavirus in vitro and in vivo.

Phytomedicine 2020 Oct 18;77:153230. Epub 2020 Apr 18.

Department of Laboratory, Dongguan Third People's Hospital, Affiliated Dongguan Shilong People's Hospital of Southern Medical University, Dongguan, Guangdong, China. Electronic address:

Background: Rotavirus (RV) is the primary causative agent for viral gastroenteritis among infants and young children worldwide. Currently, no clinically approved and effective antiviral drug for the treatment of RV infection is available.

Purpose: We investigated the potential anti-RV activity of resveratrol and underlying mechanisms by which resveratrol acted against RV.

Methods: The anti-RV activity of resveratrol in vitro was evaluated using plaque reduction assays. The effects of resveratrol on yield of virion progeny, viral polyprotein expression and genomic RNA synthesis were respectively investigated using enzyme-linked immunosorbent assays, western blotting and qRT-PCR assays. Further, we also measured the antiviral effect of resveratrol by evaluation of antigen clearance and assessment of changes in proinflammatory cytokines/chemokines in RV-infected neonatal mouse model.

Results: Our results indicated that 20 μM of resveratrol significantly inhibited RV replication in Caco-2 cell line by suppressing RV RNA synthesis, protein expression, viroplasm plaque formation, progeny virion production, and RV-induced cytopathy independent of the different strains and cell lines of RV that we used. Analysis of the effect of time post-addition of resveratrol indicated that its application inhibited early processes in the RV replication cycle. Further study of the underlying mechanism of anti-RV activity indicated that resveratrol inhibited RV replication by suppressing expression of heat-shock protein 90 (HSP90) mRNA and protein, and that the effect occurred in a dose-dependent manner. Overexpression of HSP90 was found to have attenuated the inhibitory effect of resveratrol on RV replication. Interestingly, the application of resveratrol were found to down-regulate the level of inhibition of RV-mediated MEK1/2 and ERK phosphorylation. Using a RV-infected suckling mice model, we found that application of resveratrol significantly lessened the severity of diarrhea, decreased viral titers, and relieved associated symptoms. Levels of mRNA expression of interleukin-2, interleukin-10, tumor necrosis factor-α, interferon-γ, macrophage inflammatory protein 1, and monocyte chemotactic protein-1 were all found to have been sharply reduced in intestinal tissue from mice which had been treated with resveratrol (10 or 20 mg/kg) after RV infection (p < 0.05).

Conclusion: These findings implied that resveratrol exhibits antiviral activity and could be a promising treatment for rotavirus infection.
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http://dx.doi.org/10.1016/j.phymed.2020.153230DOI Listing
October 2020

Author Correction: Chromosomal translocation-derived aberrant Rab22a drives metastasis of osteosarcoma.

Nat Cell Biol 2020 Jul;22(7):907

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41556-020-0541-9DOI Listing
July 2020

Chromosomal translocation-derived aberrant Rab22a drives metastasis of osteosarcoma.

Nat Cell Biol 2020 07 1;22(7):868-881. Epub 2020 Jun 1.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.

Osteosarcoma is a type of aggressive malignant bone tumour that frequently metastasizes to lungs, resulting in poor prognosis. However, the molecular mechanisms of lung metastasis of osteosarcoma remain poorly understood. Here we identify exon-intron fusion genes in osteosarcoma cell lines and tissues. These fusion genes are derived from chromosomal translocations that juxtapose the coding region for amino acids 1-38 of Rab22a (Rab22a) with multiple inverted introns and untranslated regions of chromosome 20. The resulting translation products, designated Rab22a-NeoFs, acquire the ability to drive lung metastasis of osteosarcoma. The Rab22a moiety governs the function of Rab22a-NeoFs by binding to SmgGDS-607, a GTP-GDP exchange factor of RhoA. This association facilitates the release of GTP-bound RhoA from SmgGDS-607, which induces increased activity of RhoA and promotes metastasis. Disrupting the interaction between Rab22a-NeoF1 and SmgGDS-607 with a synthetic peptide prevents lung metastasis in an orthotopic model of osteosarcoma. Our findings may provide a promising strategy for a subset of osteosarcoma patients with lung metastases.
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http://dx.doi.org/10.1038/s41556-020-0522-zDOI Listing
July 2020

Plasmonic Z-scheme Pt-Au/BiVO photocatalyst: Synergistic effect of crystal-facet engineering and selective loading of Pt-Au cocatalyst for improved photocatalytic performance.

J Colloid Interface Sci 2020 Jun 24;570:232-241. Epub 2020 Feb 24.

Department of Chemistry, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan 430070, PR China; State Key Laboratory of Silicate Materials for Architectures, Wuhan University of Technology, Wuhan 430070, PR China. Electronic address:

Constructing Z-scheme photocatalysts is one of the most effective technologies to enhance the photocatalytic reduction or oxidation ability in artificial photosynthesis. For the BiVO photocatalyst, it usually shows limited photocatalytic ability because of the severe bulk recombination of photogenerated carriers and the poor reduction reaction of photogenerated electrons. In this paper, a novel plasmonic Z-scheme Pt-Au/BiVO single-crystal photocatalyst was constructed to solve the above issues. Here, Au nanoparticles are selectively deposited on the electron-rich (0 1 0) facet of BiVO, while Pt nanoparticles are selectively modified on the Au surface. Photocatalytic results indicated that the resultant Pt-Au/BiVO Z-scheme photocatalyst exhibits an obviously higher photocatalytic performance than pure BiVO, Au/BiVO, randomly deposited BiVO(Pt-Au/BiVO(R)) and conventional Pt-Au/BiVO. More importantly, compared with the well-known Pt/BiVO(2.0 wt%), the Pt-Au/BiVO not only exhibits a higher photocatalytic performance, but also loads a lower amount of high-cost Pt cocatalyst. The excellent photocatalytic activity of the plasmonic Z-scheme Pt-Au/BiVO photocatalyst can be attributed to the synergistic effect of crystal-facet engineering and selective loading of Pt-Au, which results in the orientation transfer of photogenerated carriers in the single-crystal BiVO, the enhanced reduction power of photogenerated electrons, and the rapid oxygen-reduction reaction on Pt cocatalyst.
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http://dx.doi.org/10.1016/j.jcis.2020.02.093DOI Listing
June 2020

Targeting the CK1α/CBX4 axis for metastasis in osteosarcoma.

Nat Commun 2020 02 28;11(1):1141. Epub 2020 Feb 28.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.

Osteosarcoma, an aggressive malignant cancer, has a high lung metastasis rate and lacks therapeutic target. Here, we reported that chromobox homolog 4 (CBX4) was overexpressed in osteosarcoma cell lines and tissues. CBX4 promoted metastasis by transcriptionally up-regulating Runx2 via the recruitment of GCN5 to the Runx2 promoter. The phosphorylation of CBX4 at T437 by casein kinase 1α (CK1α) facilitated its ubiquitination at both K178 and K280 and subsequent degradation by CHIP, and this phosphorylation of CBX4 could be reduced by TNFα. Consistently, CK1α suppressed cell migration and invasion through inhibition of CBX4. There was a reverse correlation between CK1α and CBX4 in osteosarcoma tissues, and CK1α was a valuable marker to predict clinical outcomes in osteosarcoma patients with metastasis. Pyrvinium pamoate (PP) as a selective activator of CK1α could inhibit osteosarcoma metastasis via the CK1α/CBX4 axis. Our findings indicate that targeting the CK1α/CBX4 axis may benefit osteosarcoma patients with metastasis.
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http://dx.doi.org/10.1038/s41467-020-14870-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048933PMC
February 2020

The PI3K subunits, P110α and P110β are potential targets for overcoming P-gp and BCRP-mediated MDR in cancer.

Mol Cancer 2020 01 17;19(1):10. Epub 2020 Jan 17.

Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA.

Background: PI3K/AKT is a vital signaling pathway in humans. Recently, several PI3K/AKT inhibitors were reported to have the ability to reverse cancer multidrug resistance (MDR); however, specific targets in the PI3K/AKT pathways and the mechanisms associated with MDR have not been found because many of the inhibitors have multiple targets within a large candidate protein pool. AKT activation is one presumed mechanism by which MDR develops during cancer treatment.

Methods: The effects of inhibiting PI3K 110α and 110β by BAY-1082439 treatment and CRISPR/Cas9 knockout were examined to determine the possible functions of BAY-1082439 and the roles of PI3K 110α and 110β in the reversal of MDR that is mediated by the downregulation of P-gp and BCRP. Inhibition of AKT with GSK-2110183 showed that the downregulation of P-gp and BCRP is independent of generalized AKT inactivation. Immunofluorescence, immunoprecipitation, MTT, flow cytometry and JC-1 staining analyses were conducted to study the reversal of MDR that is mediated by P-gp and BCRP in cancer cells. An ATPase assay and a structural analysis were also used to analyze the potential mechanisms by which BAY-1082439 specifically targets PI3K 110α and 110β and nonspecifically influences P-gp and BCRP.

Results: By inhibiting the activation of the PI3K 110α and 110β catalytic subunits through both the administration of BAY-1082439 and the CRISPR/Cas9 deletion of Pik3ca and Pik3cb, the ATP-binding cassette transporters P-gp/ABCB1 and BCRP/ABCG2 were downregulated, thereby reestablishing the drug sensitivity of human epidermoid carcinoma and non-small cell lung cancer (NSCLC) MDR cells. Inhibition of AKT did not reverse the MDR mediated by P-gp or BCRP. The ABC family proteins and AKT may play MDR-enhancing roles independently.

Conclusions: The reversal of the dual functions of ABC-transporter-mediated and AKT-activation-enhanced MDR through the inhibition or knockout of PI3K 110α or 110β promises to improve current strategies based on combined drug treatments to overcome MDR challenges.
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http://dx.doi.org/10.1186/s12943-019-1112-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966863PMC
January 2020

A sensitive sensor based on MOFs derived nanoporous carbons for electrochemical detection of 4-aminophenol.

Ecotoxicol Environ Saf 2020 Mar 15;191:110194. Epub 2020 Jan 15.

School of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, China; Key Laboratory of Hunan Province for Water Environment and Agriculture Product Safety, Changsha, 410083, China. Electronic address:

A novel electrochemical sensor based on zinc oxide/nitrogen doped porous carbons (ZnO/NPC) modified electrode has been constructed for detecting 4-aminophenol (4-AP). The ZnO/NPC material was synthesized by one-step carbonization of MOF-5-NH. The modified glassy carbon electrode (ZnO/NPC/GCE) holds excellent electrocatalytic activity toward 4-AP, with a sensitivity of about 31.02 μA/μM/cm. Under optimal conditions, its oxidation peak current increases linearly with the increasing concentration of 4-AP (from 5 to 120 μmol/L), and the detection limits is 0.014 μmol/L (S/N = 3). Furthermore, favorable selectivity, superior reproducibility and outstanding stability have been achieved. The ZnO/NPC/GCE has been applied in detecting 4-AP in industrial waste water and achieved positive results with the recovery of 4-AP ranging from 94.02% to 107.7%, which confirms that this sensor is a reliable platform for the detection of 4-AP in waste water.
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http://dx.doi.org/10.1016/j.ecoenv.2020.110194DOI Listing
March 2020

Effect of quercetin supplementation on plasma lipid profiles, blood pressure, and glucose levels: a systematic review and meta-analysis.

Nutr Rev 2020 08;78(8):615-626

Department of Laboratory, Dongguan Third People's Hospital, Affiliated Dongguan Shilong People's Hospital of Southern Medical University, Dongguan, Guangdong, China.

Context: Clinical trials examining the cardiovascular protective effects of quercetin in humans have reported conflicting results.

Objective: The aim of this systematic review was to summarize evidence of the effects of quercetin supplementation on plasma lipid profiles, blood pressure (BP), and glucose levels in humans by performing a meta-analysis of randomized controlled trials.

Data Sources: MEDLINE, Embase, and Scopus databases were searched electronically from their inception to July 2018 to identify randomized controlled trials that assessed the impact of quercetin on lipid profiles, BP, and glucose levels.

Study Selection: Randomized controlled trials assessing the effects of quercetin or a standardized quercetin-enriched extract on plasma lipid profiles, BP, and glucose levels in humans were eligible for inclusion.

Data Extraction: A random-effects model was used for data analysis. Continuous variables were expressed as weighted mean differences (WMDs) and 95%CIs. Subgroup analyses were conducted to explore possible influences of study characteristics. Sensitivity analyses were also performed, as were analyses of publication bias.

Results: Seventeen trials (n = 896 participants total) were included in the overall analysis. Pooled results showed that quercetin significantly lowered both systolic BP (WMD, -3.09 mmHg; 95%CI, -4.59 to -1.59; P = 0.0001) and diastolic BP (WMD, -2.86 mmHg; 95%CI, -5.09 to -0.63; P = 0.01). Neither lipid profiles nor glucose concentrations changed significantly. In subgroup analyses, significant changes in high-density lipoprotein cholesterol and triglycerides were observed in trials with a parallel design and in which participants consumed quercetin for 8 weeks or more.

Conclusion: Quercetin intake resulted in significantly decreased BP in humans. Moreover, participants who consumed quercetin for 8 weeks or more showed significantly changed levels of high-density lipoprotein cholesterol and triglycerides in trials with a parallel design.
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http://dx.doi.org/10.1093/nutrit/nuz071DOI Listing
August 2020

Current risk factors for HIV infection among blood donors in seven Chinese regions.

Transfusion 2020 02 8;60(2):326-333. Epub 2020 Jan 8.

Department of Pathology, Stanford University, Palo Alto, California.

Background: In China, there is a rising concern on the increasing trends of HIV infections in high-risk groups, who make blood donations that might potentially challenge the blood safety. Analyses on current risk factors for HIV infection among Chinese blood donors are urgently needed for developing effective strategies to defer high-risk donors and to warrant the safety of the blood supply.

Study Design And Methods: We recruited 313 HIV-positive and 762 HIV-negative donors from seven study sites in China and evaluated donor demographic characteristics, current medical and behavioral risk factors associated with HIV infection in a case-control survey. Univariable analyses examined the relationship between HIV infection and donor and donation characteristics, medical and behavioral risks, living conditions, and lifestyles. Multivariable logistic regression analyses evaluated the association between selected individual risks and HIV infection. Regression tree analysis was used to select covariates correlated with both HIV infection and individual risks and thus need to be controlled for in logistic regression models.

Results: Being a man who has sex with men was associated with the highest odds of HIV infection. Not using a condom, having sex with HIV-infected individuals, having sex partners with sexually transmitted diseases (STDs), having more than two concurrent sex partners, or having an STD were all associated with more than five times higher odds of having HIV. Having remunerated sex was associated with a 2.4 increased odds of having HIV infection.

Conclusion: High-risk sexual behaviors were among the major risks for HIV infection among Chinese blood donors.
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http://dx.doi.org/10.1111/trf.15659DOI Listing
February 2020

HIV prevalence and incidence estimates among blood donors in five regions in China.

Transfusion 2020 01 16;60(1):117-125. Epub 2019 Dec 16.

Stanford University, Stanford, California.

Background: Previous data, although scant, indicated that the incidence of HIV in China has increased over the past decade. There is a growing concern about the impact of the HIV epidemic on blood safety.

Methods And Materials: We used donation data from five geographically-disperse blood centers in 2013-2016 participating in the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) China program to estimate HIV prevalence and incidence among blood donors. Multivariable logistic regression model was used to examine factors associated with HIV infection in Chinese blood donors.

Results: The overall HIV prevalence among first-time donors from 2013 through 2016 was 68.04 per 100,000 donors (95% CI 61.68-74.40). The HIV incidence rate was estimated to be 37.93 per 100,000 person-years (95% CI 30.62-46.97) among first-time donors and 20.55 per 100,000 person-years (95% CI 16.95-24.91) among repeat donors. There was substantial variation in HIV prevalence and incidence rates across blood centers. Multivariable logistic regression results showed that among first-time donors, being male, older than 25 years, minority ethnicity, less than college education, and certain occupations (commercial services, factory workers, retired, unemployed, or self-employed) were associated with positive HIV confirmatory testing results.

Conclusion: HIV prevalence and incidence among blood donors remain low in the selected five regions in China; however, an increasing trend is observed at some blood centers. It is important to monitor HIV epidemiology in Chinese blood donors on a continuous basis, especially among populations and regions of higher risk.
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http://dx.doi.org/10.1111/trf.15636DOI Listing
January 2020

Tetrandrine Interaction with ABCB1 Reverses Multidrug Resistance in Cancer Cells Through Competition with Anti-Cancer Drugs Followed by Downregulation of ABCB1 Expression.

Molecules 2019 Nov 30;24(23). Epub 2019 Nov 30.

Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA.

The overexpression of ABC transporters induced by anticancer drugs has been found to be the main cause of multidrug resistance. It is actually also a strategy by which cancer cells escape being killed. Tetrandrine is a natural product extracted from the stem of . In this study, tetrandrine showed synergistic cytotoxic activity in combinational use with chemotherapeutic drugs, such as Doxorubicin, Vincristine, and Paclitaxel, in both drug-induced and gene-transfected cancer cells that over-expressed ABCB1/P-glycoprotein. Tetrandrine stimulated P-glycoprotein ATPase activity, decreased the efflux of [H]-Paclitaxel and increased the intracellular accumulation of [H]-Paclitaxel in KB-C2 cells. Furthermore, SW620/Ad300 and KB-C2 cells pretreated with 1 μM tetrandrine for 72 h decreased P-glycoprotein expression without changing its cellular localization. This was demonstrated through Western blotting and immunofluorescence analysis. Interestingly, down-regulation of P-glycoprotein expression was not correlated with gene transcription, as the mRNA level exhibited a slight fluctuation in SW620/Ad300 and KB-C2 cells at 0, 24, 48, and 72 h treatment time points. In addition, molecular docking analysis predicted that tetrandrine had inhibitory potential with the ABCB1 transporter. Our results suggested that tetrandrine can antagonize MDR in both drug-selected and gene-transfected cancer cells by down regulating the expression of the ABCB1 transporter, followed by increasing the intracellular concentration of chemotherapeutic agents. The combinational therapy using tetrandrine and other anticancer drugs could promote the treatment efficiency of drugs that are substrates of ABCB1.
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http://dx.doi.org/10.3390/molecules24234383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930469PMC
November 2019

Upregulation of Yy1 Suppresses Dilated Cardiomyopathy caused by Ttn insufficiency.

Sci Rep 2019 11 8;9(1):16330. Epub 2019 Nov 8.

Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore.

Truncating variants in TTN (TTNtv), coding for the largest structural protein in the sarcomere, contribute to the largest portion of familial and ambulatory dilated cardiomyopathy (DCM). TTN haploinsufficiency caused by TTNtv is suggested as the disease mechanism. However, it is unclear whether TTN insufficiency causes DCM. Moreover, it is unknown whether modulation of downstream pathways serves as a therapeutic strategy for DCM caused by TTN insufficiency. Here, we show that reduction of cardiac Ttn expression by adeno-associated virus mediated shRNA (Ttn shRNA) generated DCM in mouse, demonstrating impaired cardiac performance, enlarged left ventricle (LV) and reduced LV wall thickness. A screen of 10 dysregulated and selected genes identified that Yin Yang 1 (Yy1) significantly suppressed DCM caused by Ttn shRNA. Gene profiling by RNAseq showed Yy1 modulated cell growth related genes. Ttn insufficiency activated cardiomyocyte cell cycle reentry by upregulating of Ccnd1 and Ccnd2. Cardiomyocytes activated by Ttn insufficiency did not advance to S phase by EdU incorporation assay. Yy1 promoted cardiomyocyte cell cycle by further enhancing Ccnd1 and Ccnd2 and increasing DNA replication without undergoing cell division. Importantly, upregulation of Ccnd1 and Ccnd2 suppressed DCM caused by Ttn insufficiency. Our findings demonstrate that DCM caused by Ttn insufficiency can be treated by therapeutically promoting cardiac cell cycle.
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http://dx.doi.org/10.1038/s41598-019-52796-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6841687PMC
November 2019

Yin Yang 1 Suppresses Dilated Cardiomyopathy and Cardiac Fibrosis Through Regulation of and .

Circ Res 2019 10 9;125(9):834-846. Epub 2019 Sep 9.

From the Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore (C.Y.T., J.X.W., P.S.C., H.T., D.L., W.C., J.J.).

Rationale: Pathogenic variations in the lamin gene () cause familial dilated cardiomyopathy (DCM). insufficiency caused by pathogenic variants is believed to be the basic mechanism underpinning -related DCM.

Objective: To assess whether silencing of cardiac causes DCM and investigate the role of Yin Yang 1 () in suppressing DCM.

Methods And Results: We developed a DCM mouse model induced by cardiac-specific short hairpin RNA. Silencing of cardiac induced DCM with associated cardiac fibrosis and inflammation. We demonstrated that upregulation of suppressed DCM and cardiac fibrosis by inducing expression and preventing upregulation of . Knockdown of upregulated attenuated the suppressive effect of on DCM and cardiac fibrosis. However, upregulation of alone was not sufficient to suppress DCM and cardiac fibrosis. Importantly, upregulation of together with silencing significantly suppressed DCM and cardiac fibrosis. Mechanistically, upregulation of regulated and reporter activities and modulated and gene expression in cardiomyocytes. Downregulation of inhibited TGF-β (transforming growth factor-β)/Smad signaling in DCM hearts. Regulation of both and further suppressed TGFβ/Smad signaling. In addition, co-modulation of and reduced CD3+ T cell numbers in DCM hearts.

Conclusions: Our findings demonstrate that upregulation of or co-modulation of and offer novel therapeutic strategies for the treatment of DCM caused by insufficiency.
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http://dx.doi.org/10.1161/CIRCRESAHA.119.314794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336364PMC
October 2019
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