Publications by authors named "Linhui Cao"

10 Publications

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The Pharmacological Activity of the Wenjing Decoction in Recurrent Spontaneous Abortion.

Evid Based Complement Alternat Med 2021 13;2021:8861394. Epub 2021 Apr 13.

Department of Traditional Chinese Medicine, Sun Yat-sen Memorial Hospital, SunYat-sen University, Guangzhou 510120, Guangdong, China.

Background: Recurrent spontaneous abortion (RSA) is intractable infertility and can be ameliorated with the use of traditional Chinese medicine preparation, the Wenjing decoction. This study aimed to identify the therapeutic mechanism of Wenjing decoction on specific target proteins involved in RSA.

Methods: Wenjing decoction contains Wuzhuyu, Danggui, Chuanxiong, Guizhi, Shengjiang, Banxia, Gancao, Ejiao, Mudanpi, Chishao, Dangshen, and Maidong. Using TCMSP and BATMAN databases, we queried for active ingredients and predicted their target proteins by BATMAN. Using the edgeR package, we analyzed the differentially expressed genes (DEGs) in the GSE121950 database between control samples and RSA ( = 3). The interaction between DEGs and the predicted target proteins was identified by the Venn diagram. Using the Cytoscape software and clusterProfiler package, enrichment analysis was conducted for the intersected target proteins. Additionally, the protein-protein interaction (PPI) network and pharmacological network were generated using the Cytoscape software.

Results: In total, 31, 2, 7, 7, 5, 13, 93, 11, 29, and 21 active ingredients were identified from Wuzhuyu, Danggui, Chuanxiong, Guizhi, Shengjiang, Banxia, Gancao, Mudanpi, Chishao, and Dangshen, respectively. Additionally, 100 intersected target proteins were revealed by the Venn diagram. Moreover, 98 functional terms and 24 pathways (including C-type lectin receptor signaling pathway, chemokine signaling pathway, leukocyte transendothelial migration, fluid shear stress, and atherosclerosis, and AGE-RAGE signaling pathway in diabetic complications) were enriched. In the PPI network, 10 proteins involved in these five pathways were identified, namely, TNF- (tumor necrosis factor-), IL-10 (interleukin-10), TLR4 (Toll-like receptor 4), JUN (Jun proto-oncogene), IL-1B (interleukin-1-beta), CYBB (cytochrome b558 heavy chain gene), PTGS2 (prostaglandin-endoperoxide synthase 2), APOE (apolipoprotein E), SPI1 (salmonella pathogenicity island 1), and MPO (myeloperoxidase) which showed higher degrees.

Conclusion: The abovementioned genes and pathways might be involved in the pharmacological activity of Wenjing decoction in RSA.
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http://dx.doi.org/10.1155/2021/8861394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060116PMC
April 2021

Radioresistant Nasopharyngeal Carcinoma Cells Exhibited Decreased Cisplatin Sensitivity by Inducing SLC1A6 Expression.

Front Pharmacol 2021 13;12:629264. Epub 2021 Apr 13.

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

Cisplatin-based regimens are commonly used for the treatment of nasopharyngeal carcinoma (NPC) in patients who receive concurrent chemoradiotherapy. The sensitivity of NPC cells to cisplatin is closely associated with the efficacy of radiation therapy. In this study, we established two radioresistant NPC cell lines, HONE1-IR and CNE2-IR, and found that both cell lines showed reduced sensitivity to cisplatin. RNA-sequence analysis showed that SLC1A6 was upregulated in both HONE1-IR and CNE2-IR cell lines. Downregulation of SLC1A6 enhanced cisplatin sensitivity in these two radioresistant NPC cell lines. It was also found that the expression of SLC1A6 was induced during radiation treatment and correlated with poor prognosis of NPC patients. Notably, we observed that upregulation of SLC1A6 led to elevating level of glutamate and the expression of drug-resistant genes, resulted in reduced cisplatin sensitivity. Our findings provide a rationale for developing a novel therapeutic target for NPC patients with cisplatin resistance.
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http://dx.doi.org/10.3389/fphar.2021.629264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077170PMC
April 2021

Characteristic of Tumor Regrowth After Gamma Knife Radiosurgery and Outcomes of Repeat Gamma Knife Radiosurgery in Nonfunctioning Pituitary Adenomas.

Front Oncol 2021 5;11:627428. Epub 2021 Mar 5.

Department of Radiotherapy, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Objective: This study aimed to report the characteristic of tumor regrowth after gamma knife radiosurgery (GKRS) and outcomes of repeat GKRS in nonfunctioning pituitary adenomas (NFPAs).

Design And Methods: This retrospective study consisted of 369 NFPA patients treated with GKRS. The median age was 45.2 (range, 7.2-84.0) years. The median tumor volume was 3.5 (range, 0.1-44.3) cm.

Results: Twenty-four patients (6.5%) were confirmed as regrowth after GKRS. The regrowth-free survivals were 100%, 98%, 97%, 86% and 77% at 1, 3, 5, 10 and 15 year, respectively. In multivariate analysis, parasellar invasion and margin dose (<12 Gy) were associated with tumor regrowth (hazard ratio [HR] = 3.125, 95% confidence interval [CI] = 1.318-7.410, p = 0.010 and HR = 3.359, 95% CI = 1.347-8.379, p = 0.009, respectively). The median time of regrowth was 86.1 (range, 23.2-236.0) months. Previous surgery was associated with tumor regrowth out of field (p = 0.033). Twelve patients underwent repeat GKRS, including regrowth in (n = 8) and out of field (n = 4). Tumor shrunk in seven patients (58.3%), remained stable in one (8.3%) and regrowth in four (33.3%) with a median repeat GKRS margin dose of 12 (range, 10.0-14.0) Gy. The actuarial tumor control rates were 100%, 90%, 90%, 68%, and 68% at 1, 3, 5, 10, and 15 years after repeat GKRS, respectively.

Conclusions: Parasellar invasion and tumor margin dose (<12 Gy) were independent risk factors for tumor regrowth after GKRS. Repeat GKRS might be effective on tumor control for selected patients. For regrowth in field due to relatively insufficient radiation dose, repeat GKRS might offer satisfactory tumor control. For regrowth out of field, preventing regrowth out of field was the key management. Sufficient target coverage and close follow-up might be helpful.
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http://dx.doi.org/10.3389/fonc.2021.627428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982800PMC
March 2021

circFOXM1 contributes to sorafenib resistance of hepatocellular carcinoma cells by regulating MECP2 via miR-1324.

Mol Ther Nucleic Acids 2021 Mar 1;23:811-820. Epub 2021 Jan 1.

Department of Hepato-Biliary Surgery, Dongguan People's Hospital, Southern Medical University, Dongguan 523000, China.

As one of the most common malignant tumors, hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths around the world. Emerging studies have indicated that circular RNAs (circRNAs), which play a crucial role in HCC pathogenesis and metastasis, are differentially expressed in HCC. However, the regulatory mechanisms of circRNA on sorafenib resistance of HCC are still unknown. In our study, we identified a novel circRNA, circFOXM1, using RNA sequencing (RNA-seq) that was increased in sorafenib-resistant HCC tissues. Functionally, circFOXM1 significantly inhibited HCC growth and enhanced sorafenib toxicity . Mechanistically, circFOXM1 acted as a sponge of microRNA (miR)-1324, which is a negative regulator of MECP2, indicating that circFOXM1 downregulation would regulate sorafenib resistance of HCC via releasing more free miR-1324 and suppressing MECP2 expression. Furthermore, miR-1324 overexpression was capable of reversing the circFOXM1-induced malignant phenotypes and elevated expression of MECP2 in HCC cells. circFOXM1 partially contributed to sorafenib resistance of HCC cells through upregulating MECP2 expression by sponging miR-1324.
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http://dx.doi.org/10.1016/j.omtn.2020.12.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868711PMC
March 2021

Initial Gamma Knife Radiosurgery for Large or Documented Growth Asymptomatic Meningiomas: Long-Term Results From a 27-Year Experience.

Front Oncol 2020 24;10:598582. Epub 2020 Nov 24.

Department of Radiotherapy, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Objective: The aims of this study were to investigate the long-term outcomes of initial Gamma Knife radiosurgery (GKRS) for large (≥20 mm) or documented growth asymptomatic meningiomas.

Design And Methods: This was a single-center retrospective study. Fifty-nine patients with large (≥20 mm) or documented growth asymptomatic meningiomas undergoing initial GKRS were enrolled. The median age was 56 (range, 27-83) years. The median time of follow-up was 66.8 (range, 24.6-245.6) months, and the median tumor margin dose was 13.0 Gy (range, 11.6-22.0 Gy).

Results: Tumors shrunk in 35 patients (59.3%) and remained stable in 23 (39.0%). One patient (1.7%) experienced radiological progression at 54 months after GKRS. The PFS was 100%, 97%, and 97% at 3, 5, and 10 years, respectively. Nine patients (15.3%) occurred new neurological symptoms or signs at a median time of 8.1 (range, 3.0-81.6) months. The symptom PFS was 90% and 78% at 5 and 10 years, respectively. Fifteen patients (25.4%) occurred peritumoral edema (PTE) at a median time of 7.2 (range, 2.0-81.6) months. One patient underwent surgical resection for severe PTE. In univariate and multivariate analysis, Only tumor size (≥25 mm) and maximum dose (≥34 Gy) were significantly associated with PTE [hazard ratio (HR)= 3.461, 95% confidence interval (CI)=1.157-10.356, p=0.026 and HR=3.067, 95% CI=1.068-8.809, P=0.037, respectively].

Conclusions: In this study, initial GKRS can provide a high tumor control rate as well as an acceptable rate of complications in large or documented growth asymptomatic meningiomas. GKRS may be an alternative initial treatment for asymptomatic meningiomas.
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http://dx.doi.org/10.3389/fonc.2020.598582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732633PMC
November 2020

Research on the Potential Mechanism of Gentiopicroside Against Gastric Cancer Based on Network Pharmacology.

Drug Des Devel Ther 2020 23;14:5109-5118. Epub 2020 Nov 23.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.

Background: Gastric cancer was still one of the commonly diagnosed cancer types and the third-most common cause of cancer-related death in the world. Gentiopicroside, which is extracted from the , is commonly used in both traditional treatment and modern clinical care; therefore, its anticancer effects have been attracted more attention. However, the systematic analysis of action mechanism of Gentiopicroside on gastric cancer (GC) has not yet been carried out.

Aim: A network pharmacology-based strategy combined with molecular docking studies and in vitro validation was employed to investigate potential targets and molecular mechanism of Gentiopicroside against GC.

Materials And Methods: Potential targets of Gentiopicroside, as well as related genes of GC, were acquired from public databases. Potential targets, and signaling pathways were determined through bioinformatic analysis, including protein-protein interaction (PPI), the Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, molecular docking and cell experiments were performed to further verify the above findings.

Results: Our findings revealed that the anticancer activity of Gentiopicroside potentially involves 53 putative identified target genes. In addition, GO, KEGG, and network analyses revealed that these targets were associated with cell proliferation, metabolic process, and other physiological processes. Furthermore, we have proved that critical compound affected the expression of CCND1, CCNE1, p-AKT and p-P38 at protein levels. These findings provide an overview of the anticancer action of Gentiopicroside from a network perspective; meanwhile, it might also set an example for future studies of other materials used in traditional Chinese medicine (TCM).

Conclusion: This study comprehensively illuminated the potential targets and molecular mechanism of Gentiopicroside against GC. It also provided a promising approach to uncover the scientific basis and therapeutic mechanism of TCM treating for disease.
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http://dx.doi.org/10.2147/DDDT.S270757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700081PMC
November 2020

Human umbilical cord mesenchymal stem cells-derived exosomal microRNA-451a represses epithelial-mesenchymal transition of hepatocellular carcinoma cells by inhibiting ADAM10.

RNA Biol 2020 Dec 31:1-16. Epub 2020 Dec 31.

Department of Hepato-Billiary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) expressing microRNAs (miRNAs) have been highlighted in human cancers. However, the detailed molecular mechanism of hucMSCs-derived exosomal miR-451a on hepatocellular carcinoma (HCC) remains further investigation. Our study aims to explore the impact of exosomal miR-451a on the progression of HCC. Expression of miR-451a and a disintegrin and metalloprotease 10 (ADAM10) in HCC tissues and adjacent normal tissues were determined. The exosomes were extracted from hucMSCs and co-cultured with Hep3B and SMMC-7721 cell lines. After the treatment of relative exosomes or exosome inhibitor GW4869 in Hep3B and SMMC-7721 cells, the paclitaxel resistance and malignant phenotypes of HCC cells were measured. Moreover, the effect of hucMSCs-derived exosomes on the expression of miR-451a and ADAM10 in HCC cells was assessed. The targeting relationship between miR-451a and ADAM10 was verified to detect the impact of ADAM10-wild type and ADAM10-mutant type (MUT) on HCC cell processes. Low expression of miR-451a and high expression of ADAM10 indicated a poor prognosis of HCC patients. MiR-451a was up-regulated while ADAM10 was down-regulated in HCC cells after co-culture with HucMSC-derived exosomes. The exosomes elevated miR-451a and inhibited ADAM10 to suppress the paclitaxel resistance, cell cycle transition, proliferation, migration and invasion, and promote apoptosis of HCC cells. ADAM10 was verified to be a target gene of miR-451a. ADAM10-MUT promoted HCC process independent of miR-451a mimic. HucMSC-derived exosomal miR-451a could restrict the epithelial-mesenchymal transition of HCC cells by targeting ADAM10, which might provide new targets for HCC treatment.
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http://dx.doi.org/10.1080/15476286.2020.1851540DOI Listing
December 2020

Bacterial diversity based on 16S rRNA and gyrB genes at Yinshan mine, China.

Syst Appl Microbiol 2008 Sep 7;31(4):302-11. Epub 2008 Jul 7.

School of Minerals Processing and Bioengineering, Central South University, Changsha, Hunan, China.

The diversity of bacterial communities at three sites impacted by acid mine drainage (AMD) from the Yinshan Mine in China was studied using comparative sequence analysis of two molecular markers, the 16S rRNA and gyrB genes. The phylogenetic analyses retrieved sequences from six classes of bacteria, Nitrospira, Alphaproteobacteria, Gammaproteobacteria, Deltaproteobacteria, Acidobacteria, and Actinobacteria, as well as sequences related to the plastid of the cyanobacterium Cyanidium acidocaldarium and also some unknown bacteria. The results of phylogenetic analyses based on gyrB and 16S rRNA were compared. This confirmed that gyrB gene analysis may be a useful tool, in addition to the comparative sequence analysis of the 16S rRNA gene, for the analysis of microbial community compositions. Moreover, the Mantel test showed that the geochemical characteristics, especially the pH value and the concentration of iron, strongly influenced the composition of the microbial communities.
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http://dx.doi.org/10.1016/j.syapm.2008.05.003DOI Listing
September 2008

Molecular diversity of 16S rRNA and gyrB genes in copper mines.

Arch Microbiol 2008 Feb 24;189(2):101-10. Epub 2007 Oct 24.

School of Minerals Processing and Bioengineering, Central South University, Changsha, Hunan, 410083, China.

The molecular diversities of the microbial communities from four sites impacted by acid mine drainage (AMD) at Dexing Copper Mine in Jiangxi province of China were studied using 16S rRNA sequences and gyrB sequences. Of the four sampled sites, each habitat exhibited distinct geochemical characteristics and the sites were linked geographically allowing us to correlate microbial community structure to geochemical characteristics. In the present study, we examined the molecular diversity of 16S rRNA and gyrB genes from water at these sites using a PCR-based cloning approach. We found that the microbial community appears to be composed primarily of Proteobacteria, Acidobacteria, Actinobacteria, Nitrospira, Firmicutes, Chlorella and unknown phylotypes. Of clones affiliated with Nitrospira, Leptospirillum ferrooxidans, Leptospirillum ferriphilum and Leptospirillum group III were all detected. Principal-component analysis (PCA) revealed that the distribution of the microbial communities was influenced greatly by geochemical characteristics. The overall PCA profiles showed that the sites with similar geochemical characteristics had more similar microbial community structures. Moreover, our results also indicated that gyrB sequence analysis may be very useful for differentiating very closely related species in the study of microbial communities.
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http://dx.doi.org/10.1007/s00203-007-0298-6DOI Listing
February 2008

Development and evaluation of 50-mer oligonucleotide arrays for detecting microbial populations in Acid Mine Drainages and bioleaching systems.

J Microbiol Methods 2007 Jul 29;70(1):165-78. Epub 2007 Apr 29.

School of Minerals Processing and Bioengineering, Central South University-Changsha, Hunan, 410083 China.

To effectively monitor microbial populations in acidic environments and bioleaching systems, a comprehensive 50-mer-based oligonucleotide microarray was developed based on most of the known genes associated with the acidophiles. This array contained 1,072 probes in which there were 571 related to 16S rRNA and 501 related to functional genes. The functional genes in the microarray were involved in carbon metabolism (158), nitrogen metabolism (72), sulfur metabolism (39), iron metabolism (68), DNA replication and repair (97), metal-resistance (27), membrane-relate gene (16), transposon (13) and IST sequence (11). Based on the results of microarray hybridizations, specificity tests with representative pure cultures indicated that the designed probes on the arrays appeared to be specific to their corresponding target genes. The detection limit was 5 ng of genomic DNA in the absence of background DNA. Strong linear relationships between the signal intensity and the target DNA were observed (r(2) approximately 0.98). Application of this type of the microarray to analyze the acidic environments and bioleaching systems demonstrated that the developed microarray appeared to be useful for profiling differences in microbial community structures of acidic environments and bioleaching systems. Our results indicate that this technology has potential as a specific, sensitive, and quantitative tool in revealing a comprehensive picture of the compositions of genes related with acidophilic microorganism and the microbial community in acidic environments and bioleaching systems, although more work is needed to improve.
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http://dx.doi.org/10.1016/j.mimet.2007.04.011DOI Listing
July 2007